Circulating lipopolysaccharide-binding protein (LBP), a metabolic endotoxemia marker, was identified as an independent predictor of atherosclerosis. Although increases in carotid intima-media thickness (CIMT) were repeatedly reported in obstructive sleep apnea (OSA), neither the role of OSA in metabolic endotoxemia nor of LBP in early atherosclerosis were explored in patients with OSA. At a tertiary university hospital we investigated the relationships between OSA, LBP and CIMT in 117 men who underwent full polysomnography and CIMT assessment by B-mode ultrasound. Circulating LBP concentrations and average CIMT increased from patients without OSA to those with mild-moderate and severe OSA (from 32.1+/-10.3 to 32.3+/-10.9 to 38.1+/-10.3 microg.ml(-1), p=0.015; from 0.52+/-0.09 to 0.58+/-0.06 to 0.62+/-0.10 mm, p=0.004, respectively). Oxygen desaturation index (ODI) was a predictor of serum LBP levels independent of age, waist-to-hip ratio (WHR), smoking, hypertension, HDL cholesterol, triglycerides and fasting glucose [p (ANOVA)=0.002, r(2)=0.154], with no independent effect of the ODI*WHR interaction term on LBP. Furthermore, serum LBP predicted CIMT independently of known risk factors of atherosclerosis including obesity (p<0.001, r(2)=0.321). Our results suggest that OSA severity contributes to metabolic endotoxemia in patients with OSA independently of obesity, and that LBP might represent a contributing factor promoting early atherosclerosis in such patients.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- endotoxemie krev diagnóza patofyziologie MeSH
- intimomediální šíře tepenné stěny * trendy MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny krev MeSH
- obstrukční spánková apnoe krev diagnóza patofyziologie MeSH
- polysomnografie metody trendy MeSH
- proteiny akutní fáze MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- transportní proteiny krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In the literature, few studies have investigated the effects of melatonin on energy metabolism in skeletal muscle in endotoxemia. We investigated the effects of melatonin on tissue structure, energy metabolism in skeletal muscle, and antioxidant level of rats with endotoxemia. We divided rats into 4 groups, control, lipopolysaccharide (LPS) (20 mg/kg, i.p., single dose), melatonin (10 mg/kg, i.p., three times), and melatonin + LPS. Melatonin was injected i.p. 30 min before and after the 2nd and 4th hours of LPS injection. Antioxidant status was determined by glutathione (GSH) measurement in the blood. Muscle tissue was stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) and histological scored. Also the sections were then stained with hematoxylin and eosin. The stained sections were visualized and photographed. Creatine, creatine phosphate, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels were investigated using high performance liquid chromatography (HPLC) in muscle tissue. In the Melatonin + LPS group, blood GSH levels were increased compared with the LPS group (P<0.01). Melatonin reduced myopathic changes in the LPS group according to the histopathologic findings. In addition, ATP values were increased compared with the LPS group (P<0.05). Our findings showed melatonin treatment prevented muscle damage by increasing ATP and GSH levels in rats with LPS induced endotoxemia.
- MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- endotoxemie krev farmakoterapie patologie MeSH
- energetický metabolismus účinky léků MeSH
- glutathion krev MeSH
- kosterní svaly účinky léků metabolismus patologie MeSH
- lipopolysacharidy MeSH
- melatonin farmakologie terapeutické užití MeSH
- náhodné rozdělení MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the study was to evaluate short-term heart rate variability (HRV) as an index of cardiac autonomic control in rats with lipopolysaccharide (LPS)-induced endotoxemia. Animals were injected intraperitoneally with LPS (100 microg/kg b.w.) and control group with an equivalent volume of saline. ECG recordings were done before (base) and 60, 120, 180, 240 and 300 min after LPS or saline administration. HRV magnitude was quantified by time and frequency-domain analysis (mean RR interval, SDRR, RMSSD, spectral powers in low (LF) and high frequency (HF) bands. Heart tissue homogenates and plasma were analyzed to determine interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and oxidative stress level (TBARS). Administration of lipopolysaccharide was followed by continuous rise in colonic body temperature compared to saline-treated controls. Endotoxemia in rats was accompanied by significant decrease in HRV spectral activity in high-frequency range at maximal body temperature (logHFpower: 1.2+/-0.5 vs. 1.9+/-0.6 ms(2), P<0.01). Increased IL-6 was found in heart tissue homogenates of LPS rats (8.0+/-0.6 vs. 26.4+/-4.8 pg/ml, (P<0.05). In conclusions, reduced HRV in HF band may indicate a decreased parasympathetic activity in LPS-induced endotoxemia as basic characteristics of altered cardiac control during response to endotoxemia.
- MeSH
- autonomní nervový systém patofyziologie MeSH
- bradykardie chemicky indukované patofyziologie MeSH
- časové faktory MeSH
- endotoxemie krev chemicky indukované patofyziologie MeSH
- interleukin-6 krev MeSH
- lipopolysacharidy * MeSH
- malondialdehyd krev MeSH
- mediátory zánětu krev MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus MeSH
- oxidační stres MeSH
- potkani Wistar MeSH
- srdce inervace MeSH
- srdeční frekvence * MeSH
- termoregulace MeSH
- TNF-alfa krev MeSH
- zánět krev chemicky indukované patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Common variable immunodeficiency (CVID), the most frequent symptomatic immunoglobulin primary immunodeficiency, is associated with chronic T cell activation and reduced frequency of CD4(+) T cells. The underlying cause of immune activation in CVID is unknown. Microbial translocation indicated by elevated serum levels of lipopolysaccharide and soluble CD14 (sCD14) has been linked previously to systemic immune activation in human immunodeficiency virus/acquired immune deficiency syndrome (HIV-1/AIDS), alcoholic cirrhosis and other conditions. To address the mechanisms of chronic immune activation in CVID, we performed a detailed analysis of immune cell populations and serum levels of sCD14, soluble CD25 (sCD25), lipopolysaccharide and markers of liver function in 35 patients with CVID, 53 patients with selective immunoglobulin (Ig)A deficiency (IgAD) and 63 control healthy subjects. In CVID subjects, the concentration of serum sCD14 was increased significantly and correlated with the level of sCD25, C-reactive protein and the extent of T cell activation. Importantly, no increase in serum lipopolysaccharide concentration was observed in patients with CVID or IgAD. Collectively, the data presented suggest that chronic T cell activation in CVID is associated with elevated levels of sCD14 and sCD25, but not with systemic endotoxaemia, and suggest involvement of lipopolysaccharide-independent mechanisms of induction of sCD14 production.
- MeSH
- aktivace lymfocytů MeSH
- B-lymfocyty imunologie MeSH
- běžná variabilní imunodeficience krev imunologie MeSH
- bronchiektazie krev MeSH
- C-reaktivní protein imunologie metabolismus MeSH
- deficience IgA krev imunologie MeSH
- dospělí MeSH
- endotoxemie krev imunologie MeSH
- granulom krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipopolysacharidové receptory krev imunologie MeSH
- lipopolysacharidy krev imunologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nemoci jater krev MeSH
- receptor interleukinu-2 - alfa-podjednotka krev imunologie MeSH
- senioři MeSH
- splenomegalie krev MeSH
- T-lymfocyty imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
