The cis(c)-9, trans(t)-11 (c9,t11) and t10,c12 isomers of conjugated linoleic acid (CLA) have been reported as agonists of peroxisome proliferator-activated receptor (PPAR) and beneficial in lipidemia and glycemia. However, it is unclear whether CLA isomers enhance or antagonize effects of conventional drugs targeting PPAR. Male Sprague-Dawley rats were fed high fat diet (HFD) for 8 weeks and treated without or with CLA, rosiglitazone or both for 4 weeks. Oral glucose tolerance and surrogate markers of insulin resistance were not significantly different for all treatments compared to untreated normal diet (ND) or HFD group, except lipoprotein levels. The combination of CLA and rosiglitazone had suppressed levels of low and high density lipoproteins (46 % and 25 %, respectively), compared to HFD-alone. Conversely, the atherogenic co-efficient of the animals received HFD or HFD+rosiglitazone+CLA was 2-folds higher than ND, HFD+rosiglitazone or HFD+CLA. Isolated aortic rings from the combined CLA and rosiglitazone treated animals were less sensitive to isoprenaline-induced relaxation among endothelium-denuded aortas with a decreased efficacy and potency (Rmax=53±4.7 %; pEC50=6±0.2) compared to endothelium-intact aortas (Rmax=100±9.9 %; pEC50=7±0.2). Our findings illustrate that the combination of CLA and rosiglitazone precede the atherogenic state with impaired endotheliumindependent vasodilatation before the onset of HFD-induced insulin resistance., B. K. Chai, Y. S. Lau, B. J. Loong, M. M. Rais, K. N. Ting, D. M. Dharmani, S. K. Mohankumar., and Obsahuje bibliografii
We assessed the effect of the previously uncovered gap junctio n protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat - dominant cataract (SHR - Dca ) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR - Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR - Dca compared with SHR (P<0.01 and P<0.05 , respectively; repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium; with no differences in expression between strains. SHR - Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basa l insulin sensitivity in muscle. There were 21 transc ripts common to the sets of 303 transcripts in kidney and 487 in heart showing >1.2-fold difference in expression between SHR and SHR - Dca. Tumor necrosis factor was the most significant upstream regulato r and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR - Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR - Dca strain, decr eases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney., O. Šeda, F. Liška, M. Pravenec, Z. Vernerová, L. Kazdová, D. Křenová, V. Zídek, L. Šedová, M. Krupková, V. Křen., and Obsahuje bibliografii
Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31-52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity., S. Argalácsová, O. Slanař, P. Vítek, P. Tesařová, H. Bakhouche, M. Dražďáková, O. Bartošová, T. Zima, L. Pertuželka., and Obsahuje bibliografii
This study extends our previous work by examining the effects of alpha2 -adrenoceptors under cold stimulation involving the increase of myogenic vascular oscillations as increases of very-low-frequency and low-frequency of the blood pressure variab ility. Forty-eight adult male Sprague-Dawley rats were randomly divided into four groups: vehicle; yohimbine; hexamethonium+yohimbine; guanethidine+yohimbine. Systolic blood pressure, heart rate, power spectral analysis of spontaneous blood pressure and he art rate variability and spectral coherence at very-low-frequency (0.02 to 0.2 Hz), low-frequency (0.2 to 0.6 Hz), and high-frequency (0.6 to 3.0 Hz) regions were monitored using telemetry. Key findings are as follows: 1) Cooling-induced pressor response was attenuated by yohimbine and further attenuated by hexamethonium+yohimbine and guanethidine+yohimbine, 2) Cooling-induced tachycardia response of yohimbine was attenuated by hexame - thonium+yohimbine and guanethidine+yohimbine, 3) Different patterns of p ower spectrum reaction and coherence value compared hexamethonium+yohimbine and guanethi-dine+yohimbine to yohimbine alone under cold stimulation. The results suggest that sympathetic activation of the postsynaptic alpha2-adrenoceptors causes vasoconstriction and heightening myogenic vascular oscillations, in turn, may increase blood flow to prevent tissue damage under stressful cooling challenge., Y.-H. Lin, Y.-P. Liu, Y.-C. Lin, P.-L. Lee, C.-S. Tung., and Obsahuje bibliografii
The goal of this study is to summarize the current knowledge on the effects of one of the essential metals, copper (Cu) on the reproductive system. The development of past four decades addressing effects of Cu on reproductive organs is reviewed. The most relevant data obtained from in vivo and in vitro experiments performed on humans and other mammals, including effects of copper nanoparticles (CuNPs) on the reproductive functions are presented. Short term Cu admi nistration has been found to exert deleterious effect on intracellular organelles of rat ovarian cells in vivo . In vitro administration in porcine ovarian granulosa cells releases insulin-like growth factor (IGF-I), steroid hormone progesterone (P4), and induces expression of peptides related to proliferation and apoptosis. Adverse effect of Cu on male reproductive functions has been indicated by the decrease in spermatozoa parameters such as concentration, viability and motility. Copper nanoparticles are capable of generating oxidative stress in vitro thereby leading to reproductive toxicity. Toxic effect of CuNPs has been evident more in male mice than in females. Even though further investigations are necessary to arrive at a definitive conclusion, Cu notably influences the reproductive functions by interfering with both male and female reproductive systems and also hampers embryo development in dose-dependent manner., S. Roychoudhury, S. Nath, P. Massanyi, R. Stawarz, M. Kacaniova, A. Kolesarova., and Obsahuje bibliografii
The aim of this study was to look for changes in the daily profile of steroid hormones after standardized food intake. Eight young women not taking contraceptives were followed from 5:30 a.m. till 9:30 p.m. before and 1 and 2 h after eating breakfast, snack, lunch, the second snack and dinner. The differences in steroid levels before and after meals were evaluated. As expected, glucose, C-peptide and ghrelin levels changed postprandially. The steroid hormones cortisol, progesterone, pregnenolone and dehydroepiandrosterone showed a decrease after main meals, whereas testosterone and dihydrotestosterone showed no significant dependence on food intake. Estrogen levels did not exhibit a significant nycthemeral rhythm, but estradiol decreased after main meals. In our study the known nycthemeral rhythm of LH, FSH, cortisol, progesterone and pregnenolone after food intake were confirmed, but significant changes after meals were also observed in the levels of cortisol, dehydroepiandrosterone, estradiol and SHBG., B. Rácz, M. Dušková, K. Vondra, M. Šrámková, M. Hill, L. Stárka., and Obsahuje bibliografii
This work discusses the clinical performance of deconjugated metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) determined in the basal first morning urine using a chromatographic method with electrochemical detection for the clinical diagnosis of pheochromocytoma (PHEO) and paraganglioma (PGL). Urine samples were collected from 44 patients (36 with PHEO, 8 with PGL) aged 54+/-17 (20-78) years (22 females, 22 males). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The control group consisted of 34 PHEO/PGL patients more than 4 months after adrenal gland surgery. All subjects in the control group were without a diagnosis of PHEO or PGL. Clinical sensitivity was 55 % for MN, 64 % for NMN, 80 % for combination of both MN and NMN, and only 23 % for 3TM. Clinical specificity calculated from the control group was 93 % for MN, 95 % for NMN, 95 % for the combination MN and NMN, and 97 % for 3TM. Cut-off values for deconjugated metanephrines in the basal urine were 310 (MN), 690 (NMN) and 250 μg/l (3MT). Chromatographic determination of deconjugated urinary metanephrines, which is simple without the necessity of special laboratory material, can serve for the screening of PHEO or PGL patients. Urine NMN and 3MT exerts an association to malignity, and all markers are associated with tumor mass. However, the principal laboratory diagnosis of PHEO or PGL must be based on plasma-free metanephrines and plasma chromogranin A with better performance in the laboratory diagnosis of PHEO or PGL., R. Bílek, T. Zelinka, P. Vlček, J. Dušková, D. Michalský, K. novák, J. Bešťák, J. Widimský Jr., and Obsahuje bibliografii
Dehydroepiandrosterone (DHEA) possesses fat-reducing effect, while little information is available on whether DHEA regulates cell proliferation and mitochondrial function, which would, in turn, affect lipid droplet accumulation in the broiler. In the present study, the lipid droplet accumulation, cell proliferation, cell cycle and mitochondrial membrane potential were analysis in primary chicken hepatocytes after DHEA treated. The results showed that total area and counts of lipid droplets were significantly decreased in hepatocytes treated with DHEA. The cell viability was significantly increased, while cell proliferation was significantly inhibited in a dose-dependent manner in primary chicken hepatocytes after DHEA treated. DHEA treatment significantly increased the cell population in S phase and decreased the population in G2/M in primary chicken hepatocytes. Meanwhile, the cyclin A and cyclin-dependent kinases 2 (CDK2) mRNA abundance were significantly decreased in hepatocytes after DHEA treated. No significant differences were observed in the number of mitochondria, while the mitochondrial membrane permeability and succinate dehydrogenase (SDH) activity were significantly increased in hepatocytes after DHEA treated. In conclusion, our results demonstrated that DHEA reduced lipid droplet accumulation by inhibiting hepatocytes proliferation and enhancing mitochondrial function in primary chicken hepatocytes., Long-Long Li, Dian Wang, Chong-Yang Ge, Lei Yu, Jin-Long Zhao, Hai-Tian Ma., and Obsahuje bibliografii
Dental composite materials often contain monomers with bisphenol A (BPA) structure in their molecules, e.g. bisphenol-A glycidyl dimethacrylate (Bis-GMA). In this study, it was examined whether dental restorative composites could be a low-dose source of BPA or alternative bisphenols, which are known to have endocrine-disrupting effects. Bis-GMA-containing composites Charisma Classic (CC) and Filtek Ultimate Universal Restorative (FU) and “BPA-free” Charisma Diamond (CD) and Admira Fusion (AF) were examined. Specimens (diameter 6 mm, height 2 mm, n=5) were light-cured from one side for 20 s and stored at 37 °C in methanol which was periodically changed over 130 days to determine the kinetics of BPA release. BPA concentrations were measured using a dansyl chloride derivatization method with liquid chromatography - tandem mass spectrometry detection. The amounts of BPA were expressed in nanograms per gram of composite (ng/g). BPA release from Bis-GMA-containing CC and FU was significantly higher compared to “BPA-free” CD and AF. The highest 1-day release was detected with FU (15.4±0.8 ng/g), followed by CC (9.1±1.1 ng/g), AF (2.1±1.3 ng/g), and CD (1.6±0.8 ng/g), and the release gradually decreased over the examined period. Detected values were several orders of magnitude below the tolerable daily intake (4 µg/kg body weight/day). Alternative bisphenols were not detected. BPA was released even from “BPA-free” composites, although in significantly lower amounts than from Bis-GMA-containing composites. Despite incubation in methanol, detected amounts of BPA were substantially lower than current limits suggesting that dental composites should not pose a health risk if adequately polymerized., Markéta Šimková, Antonín Tichý, Michaela Dušková, Pavel Bradna., and Obsahuje bibliografii