• MeSH
• autonomní nervový systém fyziologie   metabolismus   MeSH
• endotoxemie etiologie   komplikace   metabolismus   patofyziologie   MeSH
• kyselina askorbová * analýza   aplikace a dávkování   farmakologie   fyziologie   metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy fyziologie   MeSH
• metabolický syndrom * komplikace   metabolismus   patofyziologie   MeSH
• oxidační stres fyziologie   MeSH
• vitamin E analýza   fyziologie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

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

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

Intestinal microcirculatory disturbances play an important role in the pathophysiology of sepsis. A neural anti-inflammatory pathway has been suggested as a potential target for therapy that may dampen systemic inflammation. The aim of this study is to investigate the effects of physostigmine, a cholinesterase inhibitor, on the intestinal microcirculation and vascular contractility in experimental endotoxemia. Endotoxemia was induced in Lewis rats by intravenous lipopolysaccharide (LPS) administration. Animals were treated with either physostigmine or saline (control) following LPS challenge. The intestinal microcirculation, including leukocyte-endothelial interaction, functional capillary density (FCD) and non-perfused capillary density (NCD), was examined by intravital microscopy (IVM) 2 hours after LPS administration. The impact of physostigmine on vascular contractility of rat aortic rings was examined by in vitro myography. Physostigmine significantly reduced the number of adhering leukocytes in intestinal submucosal venules (V1 venules: -61%, V3 venules: -36%) of LPS animals. FCD was significantly increased by physostigmine treatment (circular muscle layer: +180%, longitudinal muscle layer: +162%, mucosa: +149%). Low concentrations of physostigmine produced significant contraction of aortic ring preparations, whereas high concentrations produced relaxation. In conclusion, physostigmine treatment significantly improved the intestinal microcirculation in experimental endotoxemia by reducing leukocyte adhesion and increasing FCD.

• MeSH
• cholinesterasové inhibitory aplikace a dávkování   terapeutické užití   MeSH
• endotoxemie metabolismus   patofyziologie   MeSH
• fysostigmin aplikace a dávkování   terapeutické užití   MeSH
• krysa rodu rattus MeSH
• mikrocirkulace účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední LEW MeSH
• sepse MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Impairment of the intestinal microcirculation in endotoxemia may cause a deterioration of the mucosal barrier function thus releasing intraluminal bacteria and their toxins into the systemic circulation. In clinical sepsis this mechanism may influence disease severity and outcome. The aim of the study was to investigate the impact of cannabinoid receptor 1 (CB1R) modulation within the intestinal microcirculation with regard to leukocyte activation and capillary perfusion, and on intestinal histology in experimental endotoxemia in rats. METHODS: Endotoxemia was induced by intravenous lipopolysaccharide (LPS) administration. We studied 5 groups of animals: controls (CON), LPS, LPS + CB1R agonist (ACEA, 2.5 mg/kg), LPS + CB1R antagonist (AM281, 2 mg/kg) and LPS + CB1R agonist (ACEA, 2.5 mg/kg) + CB1R antagonist (AM281, 2 mg/kg). Intestinal intravital microscopy (IVM) was performed two hours following LPS/placebo administration. Intestinal leukocyte adhesion in submucosal venules and functional capillary density (FCD) of the intestinal wall was quantified using IVM. Histological changes were assessed using a standardized injury score. RESULTS: After two hours of endotoxemia, we observed a significant increase of leukocyte adhesion in intestinal submucosal venules. Administration of the CB1R antagonist in endotoxemic animals significantly reduced the number of adhering leukocytes (p < 0.05). The CB1R agonist did not further increase leukocyte adhesion. FCD was significantly improved by the CB1R antagonist (p < 0.05). Administration of the CB1R agonist, ACEA, reversed the beneficial effect of the CB1R antagonist, AM281. CONCLUSIONS: CB1R inhibition significantly improved intestinal microcirculation by reducing leukocyte adhesion and increasing FCD in acute endotoxemia in rats. The data supports the involvement of the CB1R signaling in leukocyte activation during sepsis. Drugs targeting the CB1R may have therapeutic potential in systemic inflammation, such as sepsis.

• MeSH
• buněčná adheze MeSH
• endotoxemie patofyziologie   MeSH
• kanabinoidy MeSH
• krysa rodu rattus MeSH
• leukocyty účinky léků   MeSH
• mikrocirkulace účinky léků   MeSH
• modely nemocí na zvířatech MeSH
• potkani inbrední LEW MeSH
• střeva krevní zásobení   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Deletion of the cellular inhibitor of apoptosis protein 2 (cIAP2) is capable of rendering lipopolysaccharide (LPS)-activated macrophages highly susceptible to apoptotic triggers, thereby quickly eliminating the resident macrophage population soon after the initiation of a systemic inflammatory response. The aim of our study was to evaluate the impact of cIAP2 deletion on leukocyte recruitment and capillary perfusion in experimental endotoxemia and polybacterial sepsis using intravital microscopy of the intestinal microcirculation, which is crucial in the pathogenesis of septic multiple organ failure. We studied six groups of animals: wild-type (WT) control mice, cIAP2 knockout mice, endotoxemic WT mice (5 mg/kg LPS), endotoxemic cIAP2 knockouts (5 or 50 mg/kg LPS, respectively), and WT as well as knockout mice with polybacterial sepsis (colon ascendens stent peritonitis [CASP]). Intravital microscopy of the intestinal microcirculation was performed after 1 h of endotoxemia or 12 h of CASP-induced sepsis, respectively. Intestinal microvascular blood flow was measured using laser Doppler flowmetry. After 1 h of endotoxemia (5 mg/kg LPS), we observed a significant increase of leukocyte adhesion in intestinal submucosal venules of WT mice in comparison with control animals. The cIAP2 knockout mice showed a significant reduction in leukocyte recruitment within the intestinal submucosal microvasculature after 5 or 50 mg/kg LPS challenge, respectively. Lipopolysaccharide-induced decrease in intestinal microvascular blood flow was not affected by cIAP2 inhibition. In CASP-induced sepsis, cIAP2 deletion had no effect on intestinal leukocyte recruitment. Deletion of cIAP2 resulted in reduced microvascular leukocyte recruitment within the intestinal microcirculation in endotoxemia but not in polybacterial sepsis.

• MeSH
• endotoxemie genetika   metabolismus   patofyziologie   MeSH
• inhibitory apoptózy genetika   metabolismus   MeSH
• mikrocirkulace genetika   fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• sepse genetika   metabolismus   patofyziologie   MeSH
• střeva krevní zásobení   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Článek popisuje současný pohled na vztah intestinální bariéry a diabetu mellitu 1. i 2. typu. Bariéra tenkého střeva je komplexním homeostatickým systémem, zahrnujícím intestinální permeabilitu, intestinální imunitu a intestinální mikrobiotu. Porucha bariérové funkce střeva, vedoucí ke zvýšenému prostupu exoantigenů, infekčních agens a dietních antigenů k slizničním imunokompetentním buňkám a do vnitřního prostředí organizmu, je dávána do souvislosti s rozvojem autoimunitního poškození beta buněk pankreatu u diabetes mellitus 1. typu, ale i do souvislosti se zvýšenou systémovou produkcí cytokinů s následným vznikem inzulínové rezistence. Naopak narušení struktury a funkce tenkého střeva v souvislosti s dlouhodobou hyperglykemií může vést k ovlivnění intestinální bariéry. Narůstající znalosti mechanizmů zahrnutých v regulaci intestinální bariéry poskytují nové možnosti v prevenci a léčbě diabetes mellitus 1. typu, 2. typu a příbuzných metabolických chorob.

This review analyses recent understanding of the role of the intestinal barrier function in the development of type 1 and type 2 diabetes. Intestinal barrier is complex homeostatic system consisting of intestinal permeability, intestinal immunity as well as intestinal microbiota. Via alterations in the intestinal permeability, intestinal barrier function becomes compromised whereby access of exoantigens, infectious agents and dietary antigens to mucosal immune response elements is facilitated, which may eventually lead to immune reactions with damage to pancreatic beta cells and can lead to increased cytokine production with consequent insulin resistance. Conversely, there is ample evidence that diabetes mellitus affects gastrointestinal morphology and function. The reinforcing the intestinal barrier can offer and open new horizons in the prevention and treatment of type 1 and type 2 diabetes.

• Klíčová slova
• intestinální bariéra, permeabilita tenkého střeva, intestinální mikrobiota, bakteriální lipopolysacharid, low grade endotoxemie,
• MeSH
• alergeny škodlivé účinky   MeSH
• autoimunitní nemoci etiologie   patofyziologie   MeSH
• beta-buňky fyziologie   imunologie   MeSH
• diabetes mellitus 1. typu patofyziologie   MeSH
• diabetes mellitus 2. typu patofyziologie   MeSH
• diabetes mellitus * etiologie   patofyziologie   MeSH
• endotoxemie etiologie   patofyziologie   MeSH
• gliadin škodlivé účinky   MeSH
• inzulinová rezistence fyziologie   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• lipopolysacharidy fyziologie   MeSH
• metagenom MeSH
• nemoci střev patofyziologie   prevence a kontrola   MeSH
• obezita etiologie   patofyziologie   prevence a kontrola   MeSH
• permeabilita MeSH
• prebiotika MeSH
• tenké střevo * fyziologie   imunologie   mikrobiologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

According to our study, diseases of the nose and paranasal sinuses were found in 59.4% of patients with acute and chronic leukemias. In chronic leukemia purulentinflammatory diseases had abortive clinical manifestation. In acute leukemia, especially during the induction of remission, purulentinflammatory diseases of the nose and paranasal sinuses were associated with significant signs of purulent process. Inflammatory diseases of the paranasal sinuses are manifested by pronounced shift of hematological indices of intoxication that indicates increase of autointoxication, disturbance of adaptation mechanisms and transition of adaptivecompensatory immunological reactions in damaging ones.

• MeSH
• endotoxemie * patofyziologie   MeSH
• leukemie * komplikace   MeSH
• lidé MeSH
• nemoci nosu * etiologie   imunologie   MeSH
• nemoci vedlejších nosních dutin * etiologie   imunologie   MeSH
• paranazální dutiny MeSH
• výzkum MeSH
• Check Tag
• lidé MeSH

The purpose of our study was to evaluate changes of the cerebral microcirculation during the early stages of endotoxemia in mechanically-ventilated rabbits using Sidestream dark-field (SDF) imaging. Images were obtained using SDF imaging from the surface of the brain via craniotomy before and after rapid administration of a high dose of endotoxin or saline (control group). Although endotoxin shock was successfully induced, we have not found any significant alteration of the cerebral microcirculation during the shock. We speculate that either the model of sepsis with a rapid high dose of endotoxin does not reflect the usual progression of septic encephalopathy or some components other than cerebral microcirculatory alteration play a role at the early stage of septic encephalopathy and the cerebral microcirculation is still preserved. Further studies are needed to clarify our findings.

• MeSH
• endotoxemie chemicky indukované   patologie   patofyziologie   terapie   MeSH
• endotoxiny MeSH
• infekce vyvolané Escherichia coli chemicky indukované   patologie   patofyziologie   terapie   MeSH
• králíci MeSH
• mikrocirkulace MeSH
• mozek krevní zásobení   patologie   patofyziologie   MeSH
• septický šok MeSH
• umělé dýchání MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Disturbance of capillary perfusions due to leukocyte adhesion, disseminated intravascular coagulation, tissue edema is critical components in the pathophysiology of sepsis. Alterations in brain microcirculation during sepsis are not clearly understood. The aim of this study is to gain an improved understanding of alterations through direct visualization of brain microcirculations in an experimental endotoxemia using intravital microscopy (IVM). Endotoxemia was induced in Lewis rats with Lipopolysaccharide (LPS, 15 mg/kg i.v.). The dura mater was removed via a cranial window to expose the pial vessels on the brain surface. Using fluorescence dyes, plasma extravasation of pial venous vessels and leukocyte-endothelial interaction were visualized by intravital microscopy 4 h after LPS administration. Plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO were evaluated after IVM. A significant plasma extravasation of the pial venous vessels was found in endotoxemia rats compared to control animals. In addition, a significantly increased number of leukocytes adherent to the pial venous endothelium was observed in septic animals. Endotoxemia also induced a significant elevation of plasma cytokine levels of IL1-β, IL-6, IFN-γ, TNF-α and KC/GRO. Endotoxemia increased permeability in the brain pial vessels accompanied by an increase of leukocyte-endothelium interactions and an increase of inflammatory cytokines in the plasma.

• MeSH
• buněčná adheze MeSH
• cévní endotel metabolismus   patofyziologie   MeSH
• endotoxemie metabolismus   patofyziologie   MeSH
• interferon gama krev   MeSH
• interleukin-1beta krev   MeSH
• interleukin-6 krev   MeSH
• kapilární permeabilita MeSH
• krysa rodu rattus MeSH
• leukocyty fyziologie   MeSH
• mikrocévy metabolismus   patofyziologie   MeSH
• mikrocirkulace fyziologie   MeSH
• mozek krevní zásobení   MeSH
• mozkové žíly metabolismus   MeSH
• potkani inbrední LEW MeSH
• TNF-alfa krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH