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Tytuł:
Examination of cyp51A and cyp51B expression level of the first Polish azole resistant clinical Aspergillus fumigatus isolate
Autorzy:
Brillowska-Dąbrowska, Anna
Mroczyńska, Martyna
Nawrot, Urszula
Włodarczyk, Katarzyna
Kurzyk, Ewelina
Powiązania:
https://bibliotekanauki.pl/articles/1038929.pdf
Data publikacji:
2015
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
Aspergillus fumigatus
azole resistance
cyp51A
cyp51B
Opis:
Aspergillus fumigatus is one of the most prevalent airborne fungal pathogens causing infections worldwide. Most A. fumigatus strains are susceptible to azoles, which are administered as the first line therapeutics. However, during last decade the acquired resistance to triazoles by these species has been described. There is a number of publications concerning the examination of clinical A. fumigatus strains from different countries, however there has been no report from Poland. Here, we describe for the first time, an examination of cyp51A and cyp51B expression level of 11 clinical A. fumigatus strains isolated during 2007-2014 period from the collection of Medical University in Wrocław. Their susceptibility to itraconazole, voriconazole and posaconazole has been examined. The MIC values of triazoles for one of the examined isolates were respectively: > 8 mg/L for itraconazole, 2 mg/L for voriconazole and 0.5 mg/L for posaconazole. The cyp51A gene with its promoter region of all isolates was sequenced. It was found that the resistant isolate harbors the TR34/L98H mutation in the cyp51A gene and when cultured on media supplemented with voriconazole exhibits overexpression of both, cyp51A and cyp51B genes. The level of cyp51A gene expression was about 50 times higher than cyp51B.
Źródło:
Acta Biochimica Polonica; 2015, 62, 4; 837-839
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Phenobarbital-induced expression of cytochrome P450 genes.
Autorzy:
Czekaj, Piotr
Powiązania:
https://bibliotekanauki.pl/articles/1044233.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
CYP2B
cytochrome P450
phenobarbital-responsive enhancer unit
CYP2H1.
orphan receptors
CYP3A
PXR
CAR
phenobarbital
Opis:
In contrast to the well-known Ah receptor-mediated regulation of the CYP1A1 gene by polycyclic aromatic hydrocarbons, the molecular mechanism by which phenobarbital (PB) and PB-like inducers affect transcription of CYP genes remains unknown; no receptor for these chemicals has been found to date. However, in the last 5 years PB-responsive sequences have been identified in the 5' flanking regions of several P450 genes. The phenobarbital-responsive enhancer unit (PBRU) of CYP2B gene family members contain two potential nuclear receptor binding sites (NR1 and NR2) that flank a nuclear factor 1 (NF-1) binding motif. The nuclear factors that regulate PBRU activity have not yet been characterized. It seems that PB may activate multiple nuclear orphan receptors to induce various CYP genes. CYP2B and CYP3A genes appear to be targets for the orphan receptors CAR and PXR, respectively. It is also possible that the pleiotropic effects of PB can, in part, be explained by the ability of the CAR-RXR heterodimer to bind to a variety of nuclear receptor binding motifs. The induction of cytochromes P450 may result in interactions between xenobiotics and in the interference of xenobiotic metabolism and endogenous signalling pathways.
Źródło:
Acta Biochimica Polonica; 2000, 47, 4; 1093-1105
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Expression of cytochrome P450 2C and 3A in female rat liver after long-term administration of gonadoliberin analogs
Autorzy:
Skowronek, Rafał
Czekaj, Piotr
Suszka-Świtek, Aleksandra
Czech, Ewa
Wiaderkiewicz, Anna
Plewka, Danuta
Bryzek, Aleksandra
Powiązania:
https://bibliotekanauki.pl/articles/2177070.pdf
Data publikacji:
2015-11-27
Wydawca:
Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
Tematy:
CYP2C
CYP3A
liver-enriched transcription factors
growth hormone
dalarelin
cetrorelix
Opis:
Objectives Gonadoliberin (GnRH) analogs may be expected to indirectly modify growth hormone (GH) total concentration and its 24-h secretion profile. As a consequence, changes in the levels of GH may modify the mechanism of sexdependent cytochromes P450 (CYP450) synthesis, including the expression of transcriptional factors. The aim of the study has been to evaluate the effect of long-term administration of a low dose of GnRH analogs on hepatic expression of CYP2C and CYP3A isoforms, and the transcription factors: pregnane X receptor (PXR), hepatocyte nuclear factor 4α (HNF4α), HNF6 and signal transducers and activators of transcription 5b (STAT5b). Material and Methods The study was carried out on adult female Sprague-Dawley rats during a 3-month treatment with dalarelin (GnRH agonist) and cetrorelix (GnRH antagonist), at a daily intraperitoneal injection (i.p.) dose of 6 μg/kg body weight/day, and 1, 2, and 4 weeks after treatment discontinuation. The concentrations of ovarian hormones and GH in the blood serum were determined by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA) method, respectively. Then, the expression of hepatic CYP450s (reverse transcription polymerase chain reaction – RT-PCR, Western blot and immunohistochemistry) and transcription factors (RT-PCR) was evaluated. Results We have found that cetrorelix induces changes in the circadian pattern of GH secretion and enhances GH blood concentrations. These changes may cause increased expression of both, female-specific CYP450s (especially CYP3A9), and HNF4α/HNF6 transcription factors. Decrease in GH blood concentrations, resulting from the effect of dalarelin, may promote inhibition of female-specific CYP2C12 and CYP3A9 isoforms as well as STAT5b transcription factor. Slight changes in sex-independent CYP3A1 protein expression caused by GnRH analogs were also observed. Conclusions In adult female rats, HNF4α/HNF6 and STAT5b seem to be crucial for the regulation of GnRH antagonist/GH- and GnRH agonist/GH-dependent pattern of CYP450 expression, respectively.
Źródło:
International Journal of Occupational Medicine and Environmental Health; 2016, 29, 2; 293-314
1232-1087
1896-494X
Pojawia się w:
International Journal of Occupational Medicine and Environmental Health
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Association of the cytochrome P450 and arylamine N-acetyltransferase gene polymorphisms with the incidence of head and neck cancer in Polish population
Autorzy:
Gogolewska, Monika
Kabziński, Jacek
Majsterek, Ireneusz
Powiązania:
https://bibliotekanauki.pl/articles/23381296.pdf
Data publikacji:
2023-12-15
Wydawca:
Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
Tematy:
xenobiotics
head and neck cancer
CYP1A
NAT2
CYP2D
NAT1
Opis:
Objectives Head and neck cancer (HNC) is one of the most common cancers. Most exogenous HNC is head and neck squamous cell carcinomas. Scientists are striving to develop diagnostic tests that will allow the prognosis of HNC. The aim of the study was to determine the risk of HNC. The research concerned changes caused by polymorphisms in genes encoding proteins responsible for the metabolism of xenobiotics. Material and Methods In group of 280 patients with HNC, the occurrence of polymorphic variants in NAT1(rs72554606), NAT2(rs1799930), CYP1A(rs1799814), CYP2D(rs3892097) were studied with TaqMan technique. The control group consisted of 260 cancer free people. The TNM scale was analyzed. Gene interactions of genotyped polymorphisms were investigated. The effects of smoking and alcohol consumption on HNC were assessed. Results The results indicated an increased risk of HNC in NAT1 polymorphisms in the GC genotype (OR = 1.772, 95% CI: 1.184–2.651, p = 0.005) and NAT2 polymorphism in the GA genotype (OR = 1.506, 95% CI: 1.023–2.216, p = 0.037). The protective phenomenon in the CYP1A polymorphism the GT genotype (OR = 0.587, 95% CI: 0.381–0.903, p = 0.015) and the TT genotype (OR = 0.268, 95% CI: 0.159–0.452, p = 0.001). The coexistence of GA-GC polymorphisms (OR = 2.687, 95% CI: 1.387–5.205, p = 0.003) in NAT2-NAT1 genes increases the risk of HNC. Risk-reducing effect in the polymorphism GG-GT (OR = 0.340, 95% CI: 0.149–0.800, p = 0.011), GG-TT (OR = 0.077, 95% CI: 0.028–0.215, p < 0.0001), GA-TT (OR = 0.250, 95% CI: 0.100–0.622, p = 0.002), AA-GT (OR = 0.276, 95% CI: 0.112–0.676, p = 0.002) in NAT2-CYP1A genes. In the CYP2D-CYP1A genes in the polymorphisms CT-CC (OR = 0.338, 95% CI: 0.132–0.870, p = 0.020), TT-GG (OR = 0.100, 95% CI: 0.027–0.359, p = 0.001), TT-GC (OR = 0.190, 95% CI: 0.072–0.502, p = 0.0004), TT-CC (OR = 0.305, 95% CI: 0.107–0.868, p = 0.024). Correlation was noted between cigarette smoking and HNC (OR = 7.297, 95% CI: 4.989–10.674, p < 0.0001) and consuming alcohol (OR = 1.572, 95% CI: 1.003–2.464, p = 0.047). Conclusions The CYP1A polymorphism shows a protective association with HNC. On the other hand, NAT2, NAT1 polymorphism influence the susceptibility to developing HNC. The coexistence of the NAT2-NAT1 genotypes increases the risk of HNC. In contrast, NAT1-CYP1A and CYP1A-CYP2D reduce this risk. Smoking and alcohol consumption increase the incidence of HNC.
Źródło:
International Journal of Occupational Medicine and Environmental Health; 2023, 36, 6; 812-824
1232-1087
1896-494X
Pojawia się w:
International Journal of Occupational Medicine and Environmental Health
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Expression of cytochrome CYP2B1/2 in nonpregnant, pregnant and fetal rats exposed to tobacco smoke.
Autorzy:
Czekaj, Piotr
Wiaderkiewicz, Anna
Florek, Ewa
Wiaderkiewicz, Ryszard
Powiązania:
https://bibliotekanauki.pl/articles/1044235.pdf
Data publikacji:
2000
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
pregnancy
CYP2B6
rats
cytochrome P450
CYP2B1/2
tobacco smoke
Opis:
Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke obtained from non-filter cigarettes. During the exposure, concentration of tobacco smoke was monitored indirectly by measuring the CO level (1500 mg/m3 air). The efficacy of exposure was assessed by measuring urine nicotine and cotinine levels. Cigarette smoke did not change total cytochrome P450 and b5 protein levels in any of the organs studied, and most of these organs did not show any changes in the activity of reductases associated with these cytochromes. Following exposure to tobacco smoke, fetal rat liver expressed CYP2B1/2 protein; in newborns (day 1) both liver and lung showed CYP2B1/2 protein expression and very low pentoxyresorufin O-dealkylase activity. Western blot analysis of adult liver, lung, heart, but not of brain microsomes, showed that tobacco smoke induced CYP2B1/2 in both nonpregnant and pregnant rats, though its expression was lower in the livers and hearts of pregnant females. In the rat and human placenta, neither rat CYP2B1/2 nor human CYP2B6 showed basal or tobacco smoke-induced expression at the protein level. This study shows clearly that the expression of CYP2B1/2, which metabolizes nicotine and some drugs and activates carcinogens, is controlled in rats by age-, pregnancy-, and tissue-specific regulatory mechanisms.
Źródło:
Acta Biochimica Polonica; 2000, 47, 4; 1115-1127
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Preliminary study on adverse effects of phenanthrene and its methyl and phenyl derivatives in larval zebrafish, Danio rerio
Autorzy:
Wolińska, L.
Brzuzan, P.
Woźny, M.
Góra, M.
Łuczyński, M. K.
Podlasz, P.
Kolwicz, S.
Piasecka, A.
Powiązania:
https://bibliotekanauki.pl/articles/363152.pdf
Data publikacji:
2011
Wydawca:
Uniwersytet Warmińsko-Mazurski w Olsztynie
Tematy:
toksyczność ostra
CYP1A
cyp1b1
geny vtg
ekspresja mRNA
stężenie nie wywołujące efektu
WWA
Real-Time qPCR
acute toxicity
cyp1a genes
cyp1b1 genes
vtg genes
mRNA expression
No Effect Concentration
PAHs
Opis:
Toxic effects of polycyclic aromatic hydrocarbons (PAHs) have been extensively studied in fish, although knowledge concerning biological activities of phenanthrene and its derivatives remains still incomplete. The aim of this work was to evaluate lethal and sublethal effects of benzo(a)pyrene, phenanthrene and phenanthrene derivatives (1-methylphenanthrene, 4-methylphenanthrene, 1-phenylphenanthrene and 4-phenylphenanthrene) on zebrafish (Danio rerio) larvae. We conducted acute toxicity test, using 96h static renewal exposure to a series of the PAH concentrations (0.05, 0.50, 5.00, 50.00µmol*l-1), to determine the No Effect Concentration (NEC) value for each compound examined. The mean NEC estimates obtained in the study were 5.16۪.45µmol*l-1 (B[a]P), 4.88۪.13µmol*l-1 (Ph), 40.24䔰.93µmol*l-1 (1P-Ph), 47.92ۭ.61µmol*l-1 (1M-Ph), 24.31۱.33µmol*l-1 (4P-Ph) and 3.11۫.01µmol*l-1 (4M-Ph) and suggested the following order of PAH toxicities on Danio rerio larvae: 4M-Ph>Ph˜B[a]P>4PPhP-Ph>1M-Ph. To gain insight into possible molecular mechanisms of apparent toxicity of phenanthrene derivatives on zebrafish larvae, we examined mRNA expression of cyp1a, cyp1b1, and vtg genes in the larvae exposed for 48h to a PAH concentration of 0.50µmol*l-1. Whereas the larvae exposed to each tested PAH displayed many developmental abnormalities (i.e. pericardial and yolk sac edema, dorsal curvature, or tail malformations), no significant upregulation of cyp1a and cyp1b1 mRNA was observed, except for zebrafish exposed to B[a]P. However, significant reduction of vtg mRNA was observed in the larvae exposed to phenanthrene and its 4P- derivative. The results may contribute to the development of a new knowledge about effects of structurally diverse phenanthrene derivatives on vertebrate organisms.
Źródło:
Environmental Biotechnology; 2011, 7, 1; 26-33
1734-4964
Pojawia się w:
Environmental Biotechnology
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Inhibition of CYP17 expression by adrenal androgens and transforming growth factor β in adrenocortical cells.
Autorzy:
Biernacka-Łukanty, Justyna
Lehmann, Tomasz
Trzeciak, Wiesław
Powiązania:
https://bibliotekanauki.pl/articles/1041500.pdf
Data publikacji:
2004
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
CYP17
adrenocortical cells
TGF-β
androgens
expression
Opis:
Cytochrome P450c17, encoded by the CYP17 gene, is a component of the 17a-hydroxylase/17,20-lyase enzyme complex essential for production of adrenal glucocorticoids and androgens as well as gonadal androgens. The expression of CYP17 in adrenocortical cells is stimulated by corticotropin (ACTH) via the signal transduction pathway involving cAMP and protein kinase A (PKA). Thus, in addition to glucocorticoids, ACTH stimulates formation of adrenal androgens, which are known to induce transforming growth factor β (TGF-β) secretion. TGF-β in turn inhibits steroid hormone output by attenuating both basal and ACTH-dependent expression of CYP17. The present study revealed that treatment of bovine and human H295R adrenocortical cells with androgens resulted in a decrease in the basal level of CYP17 transcript and cortisol secretion, without affecting forskolin-stimulated levels. We also demonstrated that in H295R cells TGF-β inhibited both basal and forskolin-stimulated accumulation of CYP17 mRNA. Determination of promoter activity, directing luciferase reporter gene expression in H295R cells transfected with deletion fragments of bovine CYP17 promoter, indicated that the -483 to -433 bp fragment of the promoter was necessary for the inhibitory action of TGF-β on CYP17 expression. It is concluded that in bovine and human adrenocortical cells, androgens inhibit basal CYP17 expression probably at the transcriptional level and independently of the effect of TGF-β.
Źródło:
Acta Biochimica Polonica; 2004, 51, 4; 907-917
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Cytochrome P4502C9 genotype in Southeast Anatolia and possible relation with some serum tumour markers and cytokines.
Autorzy:
Yılmaz, Necat
Erbağcı, Ayşe
Aynacioğlu, A
Powiązania:
https://bibliotekanauki.pl/articles/1044109.pdf
Data publikacji:
2001
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
CYP2C9 polymorphism
Anatolia
cytokines
tumour markers
Opis:
Substrates for CYP2C9 include fluoxetine, phenytoin, warfarin, losartam and numerous nonsteroidal anti-inflammatory drugs. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino-acid residues 144 Arg/Cys and 359 Ile/Leu of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, the frequency of this allele is, however, rather low. Consistently with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. The polymorphic enzyme CYP2C9 takes part in the metabolism of alkylating agents and polycyclic aromatic hydrocarbons like benzo(a)pyrene, a carcinogen present in tobacco smoke. Although the impact of impaired enzyme activity in metabolism of carcinogens and procarcinogens has not been fully defined, an association of CYP2C9 variant alleles to DNA adduct levels in lung tissues as well as to lung cancer risk have been reported. In this study 64 healthy subjects (44M/22F) were analysed for CYP2C9 genotype with PCR-RFLP and for serum carcinoembryonic antigen (CEA), α-fetoprotein (AFP), CA 19-9, CA 15-3, ferritin, IL-6, IL-8 concentrations by chemiluminescence or electrochemiluminescence methods. CYP2C9*1 was found to be the most prevalent allele and CYP2C9*1/CYP2C9*1 was the most frequent genotype represented in 64% of the population in southeastern Anatolia (Gaziantep). Although slight differences in serum tumour marker and cytokine concentrations were observed for CYP2C9 genotypes the differences were statistically insignificant (P >0.05). This could be due to the complexity of the role of CYP2C9 in benzo(a)pyrene metabolism as well as from other contributing factors like interindividual variability of diverse enzymes participating in the same metabolic pathway, unequal expression of the variant alleles and differences in exposure to carcinogens. However, determination of CYP2C9 phenotypes in a larger group of subjects might clarify these slight differences.
Źródło:
Acta Biochimica Polonica; 2001, 48, 3; 775-782
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The effect of indole-3-carbinol on the expression of CYP1A1, CYP1B1 and AhR genes and proliferation of MCF-7 cells
Autorzy:
Ociepa-Zawal, Marta
Rubiś, Błażej
Łaciński, Mariusz
Trzeciak, Wiesław
Powiązania:
https://bibliotekanauki.pl/articles/1041121.pdf
Data publikacji:
2007
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
p21
AhR
CYP
cell proliferation
estrone hydroxylation
xenoestrogens
Opis:
The influence of an antiestrogen, indole-3-carbinol (I3C) on the expression of CYP1A1, CYP1B1 and AhR genes was investigated in an attempt to establish whether I3C could increase the expression of genes involved in estrone metabolism. Another purpose was to examine the proliferation of an estrogen-dependent breast cancer cell (MCF-7 line) under the influence of I3C and both I3C and DDT. In MCF-7 cells incubated with I3C or I3C and DDT combined, quantitative RT-PCR analysis revealed a significant increase in the level of CYP1A1, AhR, and CYP1B1 transcripts. The proliferation rate of MCF-7 cells was increased by treatment with DDT or estradiol (E2), whereas I3C did not affect the proliferation of MCF-7 cells but greatly reduced the stimulatory effect of DDT, and abolished the effect of E2. The level of p21 transcript, encoding p21 protein involved in the cell cycle, was increased several-fold by I3C comparing to its level in cells incubated with estradiol or DDT. The results suggest that the proliferation of MCF-7 cells is accompanied not only by expression of genes encoding cytochromes involved in estrogen metabolism, but also by changes in the expression of other genes including that encoding p21 protein involved in the cell cycle.
Źródło:
Acta Biochimica Polonica; 2007, 54, 1; 113-117
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Wybrane farmakokinetyczne interakcje leków w trakcie leczenia padaczki. Część II
Selected pharmacokinetic drug interactions during treatment of epilepsy. Part II
Autorzy:
Jastrzębski, Karol
Kacperska, Magdalena Justyna
Kozera-Kępiniak, Alicja
Klimek, Andrzej
Powiązania:
https://bibliotekanauki.pl/articles/1053388.pdf
Data publikacji:
2013
Wydawca:
Medical Communications
Tematy:
CYP2C19
CYP2C9
CYP2D6
CYP2E1
CYP3A4
UDP- glucuronosyltransferases
elimination
glucuronidation
metabolism of drugs
reaction of the second phase
the reaction of the first phase oxidation of drugs
valproic acid
metabolizm leków
reakcja pierwszej fazy
oksydacja leków
reakcja drugiej fazy
glukuronidacja
kwas walproinowy
eliminacja leku
UDP-glukuronylotransferazy
Opis:
Epilepsy is a disease of unknown cause to the end, mainly characterized by the occurrence of unprovoked seizures. A seizure is a temporary change, in turn, reactivity or physiological change in part or whole brain. Seizures are divided into partial, generalized and unclassified. The concept of drug-resistant epilepsy may seem somewhat obvious and intuitively understandable, but not yet developed a detailed definition of commonly accepted. As a result, doctors and researchers use very different criteria and, in some cases, even give up the precise criteria, which makes it difficult to compare the results of clinical trials and the development of practical guidelines. In the treatment of epilepsy, there is no one standard way to proceed. The aim of epilepsy treatment is complete seizure control and getting the least side effects during treatment with antiepileptic drugs. The drug should be tailored to the type of seizure or epilepsy syndrome, the frequency and severity of seizures. The choice depends on the type of drug seizures, for example, primary generalized seizures, valproic acid is used, and secondarily generalized seizures and partial carbamazepine. Older-generation drugs (phenytoin, phenobarbital, primidone) is slowly becoming obsolete. However, may be prescribed for specific indications. There is also a large group of new drugs (lamotrigine, vigabatrin, oxcarbazepine, gabapentin, levetiracetam, felbamat, topiramate, tiagabine), which are becoming increasingly popular. The emergence of a new generation of drugs gave them some advantage over older-generation drugs. They are characterized by greater specificity of action, improved pharmacokinetic properties, better evaluation of clinical trials and less side effects. These drugs are in clinical trials, and direct observation of lessons can be drawn that they are very useful in some types of epilepsy. There is no doubt that further research and observation. This article presents a brief overview of the pharmacokinetic properties of selected drugs as well as potential interactions between them. Properly processes of absorption, metabolism, distribution and elimination of drugs determine the appropriate therapeutic efficacy. The success of treatment can also significantly affect the pharmacokinetic and pharmacodynamic interactions.
Padaczka to choroba o nieznanej do końca etiologii, charakteryzująca się występowaniem nieprowokowanych napadów padaczkowych. Napad padaczkowy to z kolei przejściowa zmiana reaktywności lub zmiana stanu fizjologicznego części bądź całego mózgu. Napady dzielą się na: częściowe, uogólnione i niesklasyfikowane. Pojęcie padaczki lekoopornej może się wydawać oczywiste i zrozumiałe, niemniej jednak nie opracowano dotychczas powszechnie uznawanej szczegółowej definicji. W efekcie lekarze i badacze stosują bardzo różne kryteria, a w niektórych przypadkach nawet rezygnują z dokładnych kryteriów, co znacznie utrudnia porównywanie wyników badań klinicznych i tworzenie wytycznych. W leczeniu padaczki nie występuje jeden standardowy sposób postępowania. Celem terapii padaczki jest całkowita kontrola napadów i uzyskanie jak najmniejszych objawów niepożądanych podczas leczenia lekami przeciwpadaczkowymi. Lek powinien być dostosowany do typu napadu lub zespołu padaczkowego, częstości i ciężkości napadów. Wybór leków zależy od rodzaju napadów, przykładowo w napadach pierwotnych uogólnionych stosowany jest kwas walproinowy, natomiast we wtórnie uogólnionych i częściowych – karbamazepina. Leki starszej generacji (fenytoina, fenobarbital, prymidon) powoli wychodzą z użycia. Mogą być jednak przepisywane z powodu indywidualnych wskazań. Jest też bardzo duża grupa nowych leków (lamotrygina, wigabatryna, okskarbazepina, gabapentyna, lewetyracetam, felbamat, topiramat, tiagabina), które stają się coraz bardziej popularne. Pojawienie się leków nowej generacji dało im pewną przewagę w stosunku do starszych leków. Cechują je: większa swoistość działania, lepsze właściwości farmakokinetyczne, lepsza ocena klinicznych prób i słabsze objawy niepożądane. Z badań klinicznych i z bezpośrednich obserwacji wynika, iż są to leki bardzo przydatne w niektórych typach padaczek. Nie ulega wątpliwości, że potrzebne są dalsze badania i obserwacje. W niniejszym artykule przedstawiono krótki przegląd właściwości farmakokinetycznych wybranych leków, a także potencjalne interakcje między nimi. Prawidłowo przebiegające procesy wchłaniania, metabolizmu, dystrybucji i eliminacji leków warunkują odpowiednią skuteczność terapeutyczną. Na powodzenie leczenia mogą także znacząco wpłynąć interakcje farmakokinetyczne i farmakodynamiczne.
Źródło:
Aktualności Neurologiczne; 2013, 13, 1; 50-55
1641-9227
2451-0696
Pojawia się w:
Aktualności Neurologiczne
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Relation of the polymorphism of cyp51A sequence and the susceptibility of Aspergillus fumigatus isolates to triazoles determined by commercial gradient test (Etest) and by reference methods
Autorzy:
Nawrot, Urszula
Sulik-Tyszka, Beata
Kurzyk, Ewelina
Mroczyńska, Martyna
Włodarczyk, Katarzyna
Wróblewska, Marta
Basak, Grzegorz
Brillowska-Dąbrowska, Anna
Powiązania:
https://bibliotekanauki.pl/articles/1038548.pdf
Data publikacji:
2017
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
Aspergillus fumigatus
triazole resistance
susceptibility testing
Etest
cyp51A sequence
Opis:
The aim of this study was to evaluate the accuracy of commercial gradient test (Etest) in the detection of triazole resistant Aspergillus fumigatus isolates using reference microdilution methods and the analysis of sequences of the cyp 51A gene. The study was performed on twenty clinical isolates which were identified as Aspergillus fumigatus based on the DNA sequences of the ITS1-2 fragment of ribosomal DNA and the β-tubulin gene, out of them seventeen isolates showed wild-type cyp51A sequence and three were positive for the mutation TR34/L98H. All isolates were tested for the susceptibility to itraconazole (ITZ), voriconazole (VOR) and posaconasole (POS) using microdilution methods, according to EUCAST and CLSI protocols, as well as using Etest. The results of microdilution and Etests were analysed separately according to clinical breakpoints (CBP) defined by EUCAST version 7.0 and epidemiological cut off values (ECV). Etest as well as reference methods excellently recognised the WT isolates, which were susceptible to all tested triazoles, regardless of the method and CBP or ECV criteria used. The Etest recognized three non-WT isolates as resistant or intermediately sensitive to ITZ and POS and one as resistant to VOR. The categorical concordance between Etests and EUCAST and Etests and the CLSI method ranged from 90 to 100%. The interpretation of the results obtained from routine A. fumigatus Etests requires great caution. The use of the confirmative examinations with reference AST methods as well as with molecular tests is recommended.
Źródło:
Acta Biochimica Polonica; 2017, 64, 4; 631-634
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Polimorfizm genetyczny wybranych alleli cytochromu CYP2D6 u pacjentów z kardiomiopatią rozstrzeniową i zapaleniem mięśnia sercowego
Genetical polymporphism of chosen CYP2D6 alleles among the patients with dilated cardiomyopathy and myocarditis
Autorzy:
Smolik, Sławomir
Domal-Kwiatkowska, Dorota
Węglarz, Ludmiła
Powiązania:
https://bibliotekanauki.pl/articles/1038397.pdf
Data publikacji:
2011
Wydawca:
Śląski Uniwersytet Medyczny w Katowicach
Tematy:
cytochrom p-450
genotypowanie
wolny metabolizer
polimorfizm cyp2d6
Opis:
Cytochrome P450 2D6 has been reported to possess variation in the encoding gene that aff ects enzymatic activity. Interindividual diff erences in CYP2D6 activity can produce adverse eff ects or lack of therapeutic eff ect under standard therapy. The aim of the study was to genotyope the chosen alleles of CYP2D6 among the patients with clinically confi rmed myocarditis or dilated cardiomyopathy. Tetra-primer PCR assays was used to detect mutations in CYP2D6 *3, *4 and *6 allelles among 53 patients. A multiplex long PCR was used to genotype CYP2D6*5 allele. Analysis showed the presence of one heterozygote for CYP2D6*3, two heterozygote for CYP2D6*6, ten heterozygote and two homozygote for CYP2D6*4 among the examined patients. One person with deletion of CYP2D6 locus was also detected. Presented methods will facilitate and accelerate the detailed pharmacogenomic analysis of CYP2D6.
Cytochrom CYP2D6 ma różne warianty sekwencji kodującego go genu, wpływające na jego aktywność enzymatyczną. Międzyosobnicze różnice w aktywności izoenzymu CYP2D6 mogą prowadzić do działań niepożądanych lub braku skuteczności terapeutycznej standardowych dawek leku. Celem pracy było genotypowanie wybranych alleli CYP2D6 w grupie pacjentów z potwierdzonym klinicznie stanem zapalnym mięśnia sercowego lub kardiomiopatią rozstrzeniową. W pracy zastosowano reakcję PCR z użyciem czterech starterów w celu detekcji alleli 3*,4* i 6* CYP2D6 w grupie 53 pacjentów. Do wykrycia allelu CY2D6*5 zastosowano długołańcuchową reakcję PCR typu multipleks. Przeprowadzona analiza wykazała w badanej grupie pacjentów obecność jednej heterozygoty dla allelu CYP2D6*3, dwóch heterozygot dla allelu CYP2D*6, dziesięciu heterozygot i dwóch homozygot dla alellu CYP2D6*4. Znaleziono także jedną osobę z delecją locus CYP2D6. Przedstawione metody ułatwiają i przyspieszają dokładną analizę farmakogenetyczną izoformy CYP2D6.
Źródło:
Annales Academiae Medicae Silesiensis; 2011, 65, 3; 34-40
1734-025X
Pojawia się w:
Annales Academiae Medicae Silesiensis
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Rola 7α- hydroksylazy cholesterolu i genu CYP7A1 w fizjologii i patologii człowieka
Role of the cholesterol 7α- hydroxylase and CYP7A1 gene in human physiology and pathology
Autorzy:
Iwanicki, Tomasz
Balcerzyk, Anna
Żak, Iwona
Powiązania:
https://bibliotekanauki.pl/articles/1039371.pdf
Data publikacji:
2010
Wydawca:
Śląski Uniwersytet Medyczny w Katowicach
Tematy:
cyp7a1
kwasy żółciowe
cholesterol
polimorfizm
polymorphism
bile acids
Opis:
Cholesterol 7α- hydroxylase (CYP7A1) belongs to the big family of cytochrome p450. Biological significance of cholesterol 7α- hydroxylase is associated with beginning of cholesterol transformation to the bile acids. CYP7A1 affinity to the cholesterol is determined by its unique protein structure, different from the other proteins of cytochrome p450 family. CYP7A1 enzyme is enoded by CYP7A1 gene localized in short arm of chromosome 8. Expression of CYP7A1 gene could be regulated by farnesoid X receptor (FXR) or by kinases, which modulate nuclear receptor`s binding abilities to the gene promoter. Polymorphic variants and mutations present in the promoter region impact on the quality properties of the enzyme. CYP7A1 gene, encoding key enzyme of the cholesterol catabolic pathway is a main candidate to the research of its association with changes of serum lipids levels. Presence of genetic variants can be associated with changed levels of total cholesterol, triglycerides and Low- density lipoproteins (LDL). Promoter polymorphism of CYP7A1 is also main candidate for the research of association with such disease entities as gallbladder stone formation, colon cancer, gallbladder cancer or atherogenic- based diseases.
7α- hydroksylaza cholesterolu (CYP7A1) jest enzymem należącym do dużej rodziny cytochromu p450. Znaczenie biologiczne 7α- hydroksylazy cholesterolu związane jest z rozpoczęciem szeregu przemian cholesterolu do kwasów żółciowych. Powinowactwo CYP7A1 do cholesterolu determinowane jest unikalną budową białka, odmienną od reszty białek rodziny cytochromu p450. Enzym ten kodowany jest przez gen CYP7A1, którego locus znajduje się na ramieniu krótkim chromosomu ósmego. Ekspresja tego genu może być regulowana przy udziale farnezylowego receptora X (FXR), bądź zachodzić poprzez szereg kinaz białkowych, modulujących zdolność przyłączania się swoistych receptorów jądrowych do promotora CYP7A1. Warianty polimorficzne i mutacje, występujące w regionie promotorowym, wpływają na właściwości jakościowe enzymu. Gen CYP7A1, kodując kluczowy enzym w katabolizmie cholesterolu, jest głównym kandydatem do badań jego związku ze zmianami w osoczowym poziomie lipoprotein. Obecność wariantów genetycznych w promotorze genu CYP7A1 może być związana ze zmienionym poziomem cholesterolu całkowitego, triacylogliceroli czy LDL (Low- Density Lipoprotein). Polimorfizm promotora genu kodującego kluczowy enzym szlaku syntezy kwasów żółciowych i usuwania cholesterolu z organizmu jest głównym kandydatem do badań asocjacyjnych z takimi jednostkami chorobowymi, jak kamica żółciowa, nowotwory jelita grubego i woreczka żółciowego czy choroby o podłożu miażdżycowym.
Źródło:
Annales Academiae Medicae Silesiensis; 2010, 64, 3-4; 48-57
1734-025X
Pojawia się w:
Annales Academiae Medicae Silesiensis
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Relative quantification of CYP1A gene expression in whitefish (Coregonus lavaretus) exposed to benzo[a]pyrene
Autorzy:
Brzuzan, P.
Jurczyk, Ł.
Łuczyński, M. K.
Góra, M.
Powiązania:
https://bibliotekanauki.pl/articles/363188.pdf
Data publikacji:
2005
Wydawca:
Uniwersytet Warmińsko-Mazurski w Olsztynie
Tematy:
ekspresja genu CYP1A
sieja
benzo(a)piren
real-time PCR
benzo(a)pyrene
Coregonus lavaretus
CYP1A gene expression
RealTime PCR
relative quantification
Opis:
The expression of CYP1A (cytochrome P4501A) can be induced by a number of aromatic compounds in teleost fishes. We developed a real-time PCR assay for measuring relative quantities (RQ) of CYP1A mRNA in whitefish (Coregonus lavaretus). To test for the usefulness of the assay we performed a treatment study, using benzo[a]pyrene (B[a]P) a model CYP1A inducer. Primers for the CYP1A gene were adapted from the literature, whereas those for [beta]-actin (endogenous control) were designed from a region that was found to be conserved among salmonid [beta]-actin genes. A group of hatchery raised whitefish, with an average body mass of 15 g and total length of 12 cm were given an intraperitoneal injection (10 mg/kg) of B[a]P in corn oil (2 mg B[a]P/ml corn oil) or corn oil alone (Control). After 48 h, whitefish liver, head kidney and brains were collected for mRNA isolation and analysis. In all three tissues sampled, CYP1A mRNA was affected by treatment with B[a]P. Head kidney tissue showed the greatest induction potential (RQ=11.00) from base levels (RQ=1.00), followed by liver (RQ=9.45), and brain (RQ=3.76). These results demonstrated that CYP1A was highly inducible by B[a]P in whitefish head kidney and liver, and to some extent, in brain tissue. The approach presented here has the advantage of providing rapid and accurate measures of CYP1A induction in various tissues of fish responding to PAH contaminant exposure.
Źródło:
Environmental Biotechnology; 2005, 1, 1; 11-15
1734-4964
Pojawia się w:
Environmental Biotechnology
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Protective effects of cassia seed ethanol extract against carbon tetrachloride-induced liver injury in mice
Autorzy:
Xie, Qing
Guo, Fang-Fang
Zhou, Wen
Powiązania:
https://bibliotekanauki.pl/articles/1039746.pdf
Data publikacji:
2012
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
carbon tetrachloride
cassia seed extract
antioxidant
CYP2E1
hepatoprotective effects
Opis:
Oxidative stress has been recognized as a critical pathogenetic mechanism for the initiation and the progression of hepatic injury in a variety of liver disorders. Antioxidants, including many natural compounds or extracts, have been used to cope with liver disorders. The present study was designed to investigate the hepatoprotective effects of cassia seed ethanol extract (CSE) in carbon tetrachloride (CCl4)-induced liver injury in mice. The animals were pre-treated with different doses of CSE (0.5, 1.0, 2.0 g/kg body weight) or distilled water for 5 days, then were injected intraperitoneally with CCl4 (0.1% in corn oil, v/v, 20 ml/kg body weight), and sacrificed at 16 hours after CCl4 exposure. The serum aminotransferase activities, histopathological changes, hepatic and mitochondrial antioxidant indexes, and cytochrome P450 2E1 (CYP2E1) activities were examined. Consistent with previous studies, acute CCl4 administration caused great lesion to the liver, shown by the elevation of the serum aminotransferase activities, mitochondria membrane permeability transition (MPT), and the ballooning degeneration of hepatocytes. However, these adverse effects were all significantly inhibited by CSE pretreatment. CCl4-induced decrease of the CYP2E1 activity was dose-dependently inhibited by CSE pretreatment. Furthermore, CSE dramatically decreased the hepatic and mitochondrial malondialdehyde (MDA) levels, increased the hepatic and mitochondrial glutathione (GSH) levels, and restored the activities of superoxide dismutase (SOD), glutathione reductase (GR), and glutathione S-transferase (GST). These results suggested that CSE could protect mice against CCl4-induced liver injury via enhancement of the antioxidant capacity.
Źródło:
Acta Biochimica Polonica; 2012, 59, 2; 265-270
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
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