BACKGROUND: Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects. MATERIAL AND METHODS: We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed. RESULTS: Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function (p = 0.015 and p = 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507, p = 0.032) was the only significant contributor in the model predicting RHI. CONCLUSIONS: In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.
- Publikační typ
- časopisecké články MeSH
Autonomic nervous system (ANS) disorders are common in multiple sclerosis (MS). Previous studies showed differences in insulin resistance (IR) and lipoprotein levels in MS subjects compared to controls. Lipolysis caused by increased sympathetic activity could be one of the possible linking mechanisms leading to dyslipidemia in MS. Our study aimed to evaluate ANS activity in the context of glucose and lipid metabolism in people with MS. We prospectively measured short-term heart rate variability (HRV), fasting lipoprotein concentrations, and calculated IR indices based on plasma glucose and insulin levels during oral glucose tolerance test (oGTT) in 32 patients with MS and 29 healthy controls matched for age, sex and body mass index in our study. There was no significant difference in HRV parameters and lipoprotein levels between MS and controls. A significant positive correlation was found between low/high-frequency power ratio (LF/HF) and triglycerides (r=0.413, p=0.021) in MS subjects but not in controls. A significantly lower whole-body insulin sensitivity index (ISIMat) was found in patients with MS compared to the control group (7.3±3.7 vs. 9.8±5.6, p=0.041). No significant correlations were found between LF/HF and IR parameters. In MS subjects, the positive correlation of LF/HF with triglycerides could reflect the effects of sympathetic activity on lipolysis. Positive correlations of sympathetic activity with increased lipoprotein levels could rather reflect processes associated with immune system activation/inflammation, than processes involved in glucose homeostasis maintenance.
- MeSH
- autonomní nervový systém patofyziologie MeSH
- dospělí MeSH
- inzulinová rezistence * MeSH
- lidé MeSH
- lipidy krev MeSH
- lipolýza * MeSH
- mladý dospělý MeSH
- prospektivní studie MeSH
- roztroušená skleróza krev patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Erectile dysfunction (ED) and diabetes mellitus (DM) share common pathophysiological risk factors including endothelial dysfunction which together with hyperglycemia contribute to the increased oxidative/glycooxidative stress. A reduced NO concentration is insufficient for relaxation processes in the penis. Chronic inflammation and endoglin are involved in the regulation of endothelial function. Adiponectin from the adipose tissue has anti-inflammatory effects. Our study aimed to investigate the relation between erectile function in patients with and without DM and the oxidative stress, hormone adiponectin, and endothelial dysfunction marker endoglin. Men (n=32) with ED evaluated by the International Index of Erectile function (IIEF-5) questionnaire (17 without DM (NDM); 15 with type 2 diabetes mellitus (DM)) and 31 controls were included. Advanced glycation end products (AGEs), 8-isoprostanes (8-isoP), protein carbonyls, antioxidant capacity, adiponectin and endoglin were determined in the blood. DM patients compared to NDM patients and controls, had increased levels of glucose, C-reactive protein, triacylglycerols, 8-isoP, AGEs, endoglin and BMI. IIEF-5 score, NO and adiponectin levels were decreased. We are the first to find out that endoglin shows a negative correlation with erectile function in NDM, but not in DM patients. Endoglin can be considered as endothelial dysfunction marker in nondiabetic men suffering from ED.
- MeSH
- adiponektin krev MeSH
- diabetes mellitus 2. typu diagnóza epidemiologie krev MeSH
- dospělí MeSH
- endoglin krev MeSH
- erektilní dysfunkce diagnóza epidemiologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- oxidační stres fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Sclerosis multiplex (SM) je chronické zápalové a neurodegeneratívne ochorenie centrálneho nervového systému. Etiológa ochorenia zostáva neobjasnená, zaraďuje sa medzi autoimunitné ochorenia. Na imunitnú poruchu vplývajú genetické a environmentálne faktory. Z environmentálnych faktorov sa v patogenéze ochorenia najčastejšie skloňuje vplyv slnečného žiarenia, hladiny vitamínu D, infekčných patogénov, ale aj vplyv diéty, obezity a zloženia črevného mikrobiómu. Oficiálne odporúčania ohľadne zloženia diéty však chýbajú. Náš článok poskytuje prehľad existujúcich dôkazov z epidemiologických, klinických a laboratórnych štúdií, že zloženie tukov v strave môže hrať významnú úlohu v patogenéze SM.
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system. The etiology is still unknown, the disease is believed to be autoimmune. The immune dysregulation is affected by genetic and environmental factors. Relation to sun exposure, vitamin D levels, exposure to infectious pathogens as well as dietary habits, obesity and GUT microbiota have all been implicated in the pathogenesis. There are however no firm recommendations regarding diet in the treatment of MS. Our review deals with the available evidence from epidemiological, clinical and laboratory studies that dietary fats may play an important role in MS pathogenesis.
- MeSH
- dietní tuky MeSH
- kardiovaskulární nemoci prevence a kontrola MeSH
- kyseliny mastné omega-3 terapeutické užití MeSH
- kyseliny mastné omega-6 terapeutické užití MeSH
- lidé MeSH
- mastné kyseliny farmakologie metabolismus MeSH
- nenasycené mastné kyseliny farmakologie metabolismus MeSH
- potravní doplňky MeSH
- roztroušená skleróza * etiologie metabolismus MeSH
- stravovací zvyklosti MeSH
- střevní mikroflóra imunologie účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Schiff base copper (II) complexes are known for their anticancer, antifungal, antiviral and anti‑inflammatory activities. The aim of the current study was to investigate biological effects of Schiff base Cu (II) complexes (0.001‑100 µmol/l)‑[Cu2(sal‑D, L‑glu)2(isoquinoline)2]·2C2H5OH (1), [Cu(sal‑5‑met‑L‑glu)(H2O)].H2O (2), [Cu(ethanol)2(imidazole)4][Cu2(sal‑D, L-glu)2(imidazole)2] (3), [Cu(sal‑D,L‑glu)(2‑methylimidazole)] (4) on the human colon carcinoma cells HT‑29, the mouse noncancerous cell line NIH‑3T3 and the human noncancerous fibroblast cell line VH10. The results suggested that Cu (II) complexes exhibit cytotoxic effects against the HT‑29 cell line, while complexes 3 and 4 were the most effective. Subsequent to 72 h of incubation, apoptosis was observed in the HT‑29 cells induced by Cu (II) complexes 1 (0.1, 1, 10 and 50 µmol/l), 2 (1, 10, 50 and 100 µmol/l), 3 (0.01, 1, 10 and 50 µmol/l) and 4 (0.01, 0.1, 1 and 10 µmol/l). The apoptotic pathways activated by the Cu (II) complexes were identified. The results indicated that complexes 2, 3 and 4 were able to induce the mitochondria‑dependent pathway of apoptosis in HT‑29 cells, while complex 1 was obsered to activate the extrinsic pathway of apoptosis. The levels of the anti‑apoptotic protein Bcl‑2 were reduced and those of the pro‑apoptotic protein Bax increased following treatment with complexes 2, 3 and 4. Complex 1 had no effect on Bax protein expression. Complexes 2 and 3 induced elevation of cytochrome c (cyt c), while complex 4 induced a time‑dependent elevation of cyt c levels. No cyt c was detected in HT‑29 cells exposed to complex 1, suggesting that Cu (II) complexes activated the extrinsic pathway of apoptosis. The results from the current study in addition to previous studies suggest that Schiff base Cu (II) complexes have potential as novel anticancer drugs.
- MeSH
- antitumorózní látky aplikace a dávkování MeSH
- apoptóza účinky léků MeSH
- buňky HT-29 MeSH
- lidé MeSH
- měď aplikace a dávkování MeSH
- mitochondrie účinky léků MeSH
- myši MeSH
- nádorové proteiny biosyntéza MeSH
- nádory tračníku farmakoterapie patologie MeSH
- proliferace buněk účinky léků MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- Schiffovy báze aplikace a dávkování MeSH
- signální transdukce účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Autophagy plays an important role in cancer cells. Targeting autophagy in cancer can provide new opportunities for drug development. METHODS: In this study we tested four Schiff base Cu(II) complexes against human breast cancer cells (MCF-7) and human non-cancerous cells (HEK-293T). We have tested their cytotoxic effect by evaluating IC50 using MTT test. To detect morphological changes of the actin fibers we have used fluorescent microscopy. To determine the type of cell death we used electrophoretic analysis and western blot analysis (protein LC3). RESULTS: IC50 values of the complexes increased with time of their influence, indicating acquired resistance of MCF-7 to the complexes. Healthy cells HEK-293T were not sensitive to the Cu(II) complexes. Compared with the control cells (cells without Cu(II) complexes) which were without morphological changes of actin fibers, Cu(II) complexes induced condensation and asymmetric conformational changes in actin filaments. To examine the type of cell death induced by the Cu(II) complexes we treated MCF-7 cells with Cu(II) complexes (1, 10, 50 and 100μmol/L) during a 72h incubation period. By electrophoresis we have not detected any DNA fragmentation. To determine whether Cu(II) complexes induced autophagy or necrotic cell death we used the western blot analysis. MCF-7 cells influenced with tested Cu(II) complexes produced LC3 protein after their 72h incubation indicating autophagy in MCF-7 cancer cells. CONCLUSIONS: Tested Schiff base copper (II) complexes have antiproliferative activity against cancer cells but not against healthy cells. They have induced autophagy in the cancer cell line MCF-7.
- MeSH
- autofagie účinky léků fyziologie MeSH
- HEK293 buňky MeSH
- lidé MeSH
- měď farmakologie toxicita MeSH
- MFC-7 buňky MeSH
- myši MeSH
- proliferace buněk účinky léků fyziologie MeSH
- Schiffovy báze farmakologie toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Oxidative stress is a phenomenon associated with imbalance between production of free radicals and reactive metabolites (e.g. superoxide and hydrogen peroxide) and the antioxidant defences. Oxidative stress in individuals with Down syndrome (DS) has been associated with trisomy of the 21st chromosome resulting in DS phenotype as well as with various morphological abnormalities, immune disorders, intellectual disability, premature aging and other biochemical abnormalities. Trisomy 21 in patients with DS results in increased activity of an important antioxidant enzyme Cu/Zn superoxide dismutase (SOD) which gene is located on the 21st chromosome along with other proteins such as transcription factor Ets-2, stress inducing factors (DSCR1) and precursor of beta-amyloid protein responsible for the formation of amyloid plaques in Alzheimer disease. Mentioned proteins are involved in the management of mitochondrial function, thereby promoting mitochondrial theory of aging also in people with DS. In defence against toxic effects of free radicals and their metabolites organism has built antioxidant defence systems. Their lack and reduced function increases oxidative stress resulting in disruption of the structure of important biomolecules, such as proteins, lipids and nucleic acids. This leads to their dysfunctions affecting pathophysiology of organs and the whole organism. This paper examines the impact of antioxidant interventions as well as positive effect of physical exercise on cognitive and learning disabilities of individuals with DS. Potential therapeutic targets on the molecular level (oxidative stress markers, gene for DYRK1A, neutrophic factor BDNF) after intervention of natural polyphenols are also discussed.
- MeSH
- antioxidancia terapeutické užití MeSH
- cvičení MeSH
- Downův syndrom farmakoterapie genetika metabolismus patofyziologie psychologie MeSH
- fenotyp MeSH
- genetická predispozice k nemoci MeSH
- kognice účinky léků MeSH
- lidé MeSH
- mozek účinky léků metabolismus patofyziologie MeSH
- oxidační stres účinky léků MeSH
- učení účinky léků MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Paraoxonase 1 (PON1) seems to have a relevant role in detoxifying processes and in atherosclerosis. The aim of this study was to determine PON1 activity, the total antioxidant capacity, as well as entire lipid profile in children for screening of possible risk of atherosclerosis development. Serum PON1 arylesterase/paraoxonase activities were determined spectrophotometrically. The total antioxidant capacity of the serum was measured by TEAC method. Parameters of lipid profile were analyzed by routine laboratory methods. It has been shown that PON1 arylesterase/ paraoxonase activities were very similar to values found in adults. In children, no significant correlation between PON1 arylesterase activity and HDL was observed. PON1 paraoxonase activity correlated only with atherogenic index. PON1 arylesterase activity was significantly higher in girls than in boys. The antioxidant capacity was inversely related to the body mass index. In this study, PON1 activity was determined in healthy children aged 11 to 12 years and we found a similarity in PON1 activities of children and adults. Moreover, the results of our study support the hypothesis that higher body weight of children may contribute to a greater risk for development of atherosclerosis in which oxidative stress plays a role.
- MeSH
- antioxidancia MeSH
- aryldialkylfosfatasa chemie izolace a purifikace MeSH
- ateroskleróza etiologie prevence a kontrola MeSH
- dítě MeSH
- finanční podpora výzkumu jako téma MeSH
- interpretace statistických dat MeSH
- lidé MeSH
- lipidové peroxidy izolace a purifikace škodlivé účinky MeSH
- lipoproteiny HDL izolace a purifikace škodlivé účinky MeSH
- rizikové faktory MeSH
- tělesná hmotnost MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
