Atrial fibrosis is considered as the basis in the development of long-standing atrial fibrillation (AF). However, in advanced heart failure (HF), the independent role of fibrosis for AF development is less clear since HF itself leads to atrial scarring. Our study aimed to differentiate patients with AF from patients without AF in a population consisting of patients with advanced HF. Myocardial samples from the right atrial and the left ventricular wall were obtained during heart transplantation from the explanted hearts of 21 male patients with advanced HF. Long-standing AF was present in 10 of them and the remaining 11 patients served as sinus rhythm controls. Echocardiographic and hemodynamic measurements were recorded prior to heart transplantation. Collagen volume fraction (CVF), transforming growth factor-beta (TGF-beta), and connective tissue growth factor (CTGF) expression in myocardial specimens were assessed histologically and immunohistochemically. The groups were well matched according to age (51.9+/-8.8 vs. 51.3+/-9.3 y) and co-morbidities. The AF group had higher blood pressure in the right atrium (13.6+/-7.7 vs. 6.0+/-5.0 mmHg; p=0.02), larger left atrium diameter (56.1+/-7.7 vs. 50+/-5.1 mm; p=0.043), higher left atrium wall stress (18.1+/-2.1 vs. 16.1+/-1.7 kdynes/m(2); p=0.04), and longer duration of HF (5.0+/-2.9 vs. 2.0+/-1.6 y, p=0.008). There were no significant differences in CVF (p=0.12), in CTGF (p=0.60), and in TGF-beta expression (p=0.66) in the atrial myocardium between the two study groups. In conclusions, in advanced HF, atrial fibrosis expressed by CVF is invariably present regardless of occurrence of AF. In addition to atrial wall fibrosis, increased wall stress might contribute to AF development in long-standing AF.
- MeSH
- diferenciální diagnóza MeSH
- endomyokardiální fibróza komplikace diagnóza patofyziologie MeSH
- fibrilace síní komplikace diagnóza patofyziologie MeSH
- kolagen metabolismus MeSH
- krevní tlak MeSH
- lidé středního věku MeSH
- lidé MeSH
- srdeční frekvence MeSH
- srdeční selhání komplikace diagnóza patofyziologie MeSH
- srdeční síně patofyziologie MeSH
- stárnutí MeSH
- transformující růstový faktor beta metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. This study is focused on addressing the mutual relationship and early signals of these mechanisms in the D-galactosamine and lipopolysaccharide (D-GalN/LPS) hepatotoxicity model, with the help of standard liver function and biochemistry tests, histology, and measurement of gene expression by RT-PCR. Intraperitoneal injection of 400 mg/kg D-GalN and 50 microg/kg LPS was able to induce hepatotoxicity in rats, as evidenced by significant increases in liver enzymes (ALT, AST) and raised bilirubin levels in plasma. Heme oxygenase-1 and nitric oxide synthase-2 gene expressions were significantly increased, along with levels of their products, bilirubin and nitrite. The gene expression of glutathione peroxidase 1 remained unchanged, whereas a decrease in superoxide dismutase 1 gene expression was noted. Furthermore, the significant increase in the gene expression of apoptotic genes Bid, Bax and caspase-3 indicate early activation of apoptotic pathways, which was confirmed by histological evaluation. In contrast, the measured caspase-3 activity remained unchanged. Overall, the results have revealed differential oxidative stress and apoptotic responses, which deserves further investigations in this hepatotoxicity model.
- MeSH
- alanintransaminasa metabolismus MeSH
- antioxidancia metabolismus MeSH
- apoptóza MeSH
- bilirubin metabolismus MeSH
- exprese genu MeSH
- galaktosamin toxicita MeSH
- glutathionperoxidasa genetika metabolismus MeSH
- hemoxygenasa-1 genetika metabolismus MeSH
- játra metabolismus účinky léků MeSH
- kaspasa 3 metabolismus MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lékové postižení jater etiologie metabolismus MeSH
- lipopolysacharidy toxicita MeSH
- oxidační stres MeSH
- oxidancia metabolismus MeSH
- potkani Wistar MeSH
- superoxiddismutasa genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The nasal and tonsillar mucosa are exposed to massive incursions of pathological microorganisms. One of the mechanisms known to prevent an invasion of pathogens is an endogenous synthesis of antimicrobial peptides, which include human beta-defensins-1, 2, 3 (HBD-1, 2, 3). The aim of this study was to demonstrate the occurrence of HBD-1, 2 and 3 in the human nasal mucosa and palatine tonsils in healthy tissues and during chronic inflammation (nasal polyposis with and without the colonization of Staphylococcus aureus and chronic tonsillitis) and to evaluate their incidence under varying conditions. Another target was to compare the occurrence of human beta-defensins in these two different entities; that is, in the nasal mucosa and in the palatine tonsil. It was assumed that the incidence of HBD-1, 2, 3 was lower in tonsils than in nasal mucosa; however, inflamed samples of tonsils and nasal mucosa showed no difference in the production of HBD-1, 2, 3. The presence of all three subfamilies of HBD was significantly lower in nasal polyps with Staphylococcus aureus positive than in the negative control.
- Klíčová slova
- beta-defensins, nasal mucosa, palatine tonsil, chronic inflammation,
- MeSH
- beta-defensiny imunologie izolace a purifikace MeSH
- financování organizované MeSH
- imunohistochemie metody využití MeSH
- kationické antimikrobiální peptidy imunologie izolace a purifikace MeSH
- krční mandle fyziologie mikrobiologie patologie MeSH
- kultivační techniky metody využití MeSH
- lidé MeSH
- nosní polypy imunologie mikrobiologie MeSH
- nosní sliznice fyziologie mikrobiologie patologie MeSH
- Staphylococcus aureus imunologie izolace a purifikace MeSH
- studie případů a kontrol MeSH
- tonzilitida diagnóza imunologie mikrobiologie MeSH
- Check Tag
- lidé MeSH
The surrounding environment contains plenty of pathogens, which represent a danger of infection. The simplest way for the pathological microorganism to enter the organism is the upper airways. Inflammation of the upper airways is among the most common and frequent diseases. This category includes nasal polyposis and chronic tonsillitis. In many cases it is associated with disorders in relation to the immune response. An inflammatory infiltration of mononuclears, eosinophils, plasma and mast cells can be found in the histological structure of the polypous as well as tonsillar mucosa. One aim of this study was to determine the expression of beta-defensins and various proteins, with a possible potential role in relation to the rise and development of those changes. Another aim was to determine the relationship between the inflammatory and malignant processes in the tonsils. The samples of nasal polyps were obtained during clinically indicated endonasal surgery from patients diagnosed with nasal polyposis (n=50). The samples of tonsils were collected during surgery from patients suffering from chronic tonsillitis (n=11) or tonsillar carcinoma (n=17). Immunohistochemical procedures for the detection of human beta-defensin 1, 2, 3 (HBD-1, 2, 3), Ki- 67, endothelial nitric oxide synthase (eNOS) and cleaved caspase 3 were performed on cryostate and paraffin sections. It was proven that HBD are secreted in fairly large amounts in cases of chronic inflammation. Their secretion during the malignant transformation is limited. This is a very probable fact that plays a role in malignant transformation in tonsillar tissue. The crucial role in the development of chronic inflammation, and maybe that of malignant transformation, is played by eNOS and its product NO molecule. eNOS and the NO molecule are involved in cell cycle regulation, in the apoptotic processes and cell proliferation, as well as in the angiogenesis and vasculogenesis. Our result confirmed that eNOS is presented in the tissues of the upper airways in both chronic inflammation and carcinomatous processes. Ki-67 and cleaved caspase 3 were used as markers of cell proliferation and apoptosis.
- MeSH
- antigen Ki-67 metabolismus MeSH
- apoptóza MeSH
- beta-defensiny metabolismus MeSH
- chronická nemoc MeSH
- fluorescenční protilátková technika nepřímá MeSH
- kaspasa 3 metabolismus MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- nosní polypy imunologie patologie MeSH
- nosní sliznice imunologie metabolismus MeSH
- proliferace buněk MeSH
- synthasa oxidu dusnatého, typ III metabolismus MeSH
- tonzilární nádory enzymologie patologie MeSH
- tonzilitida enzymologie patologie MeSH
- zánět etiologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The aim of this work was to study the effects of resveratrol (RES) as compared to silymarin (SM) pretreatments on tert-butylhydroperoxide (tBH) induced apoptotic/necrotic markers in hepatocytes. Hepatocyte in cultures (48 h) and in perifused immobilized agarose threads (5h) were used as cellular systems. Hepatocyte apoptosis was estimated morphologically using Annexin-V combined with propidium iodide, or toluidine blue staining. Hepatocyte viability and functionality were evaluated by ALT and urea synthesis. Nitric oxide (NO) and carbon monoxide involvements were also examined. Resveratrol and silymarin reduced tBH-induced hepatocyte toxic effects in short term experiments (5h) as measured by a significant reduction in ALT and NO increase produced by tBH. Both inducible nitric oxide synthase (NOS-2) and hemoxygenase-1 (HO-1) gene expression were increased by tBH and reduced by both RES and SM pretreatments. Morphologically, there were ameliorations in both apoptotic and necrotic markers under RES treatment and were similar to biochemical findings. In addition, RES improved hepatocyte stability in both cellular systems. It may be concluded that resveratrol and sylimarin ameliorative effects on tBH hepatocyte toxicity are comparable; involve NOS-2 and HO-1 expression and should be re-evaluated in various in vitro and in vivo experimental conditions.
- MeSH
- alanintransaminasa MeSH
- analýza rozptylu MeSH
- apoptóza účinky léků MeSH
- cytoprotekce MeSH
- financování organizované MeSH
- hemoxygenasa-1 metabolismus MeSH
- hepatocyty metabolismus účinky léků ultrastruktura MeSH
- imobilizované buňky MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- nádorové biomarkery metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- potkani Wistar MeSH
- silymarin farmakologie MeSH
- stilbeny farmakologie MeSH
- synthasa oxidu dusnatého, typ II metabolismus MeSH
- terc-butylhydroperoxid toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
The goal of study was directed to investigate the effects of resveratrol (RES) pretreatment on the enhancing action of D-galactosamine (D-GalN; 800 mg/kg) on lipopolysaccharide (LPS; 0.5 microg/kg) inducing liver failure in rats. Liver function was assessed by determination of plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-glutathione S-transferase (alpha GST) and bilirubin (BILI). Plasma NO(2)(-) was assessed by NO(2)(-)/NO(3)(-) colorimetric kit. The estimation of nonenzymatic and enzymatic antioxidants (glutathione and catalase) was performed in plasma and liver homogenate. Lipid peroxidation was evaluated by the thiobarbituric acid reacting substances (TBARS) and the conjugated dienes (CD). Morphological examinations using light and electron microscopy were performed. Observations related to pharmacological increases of inducible nitric oxide synthase (NOS-2)/nitric oxide (NO) and inducible heme oxygenase (HO-1) in fulminant hepatic failure and modulation by resveratrol were followed up by real-time reverse transcription PCR (RT-PCR) in liver tissue. In the present study we found that among the mechanisms responsible for the hepatoprotective effect of resveratrol in the LPS/D-GalN liver toxicity model are reduction in NO, downregulation of NOS-2, modification of oxidative stress parameters and modulation of HO-1 which led to overall improvement in hepatotoxic markers and morphology after the hepatic insult.
- MeSH
- antioxidancia farmakologie MeSH
- cytoprotekce MeSH
- galaktosamin toxicita MeSH
- hemová oxygenasa (decyklizující) genetika metabolismus MeSH
- játra enzymologie patologie účinky léků MeSH
- krysa rodu rattus MeSH
- lékové postižení jater patologie prevence a kontrola MeSH
- lipopolysacharidy toxicita MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- potkani Wistar MeSH
- selhání jater chemicky indukované prevence a kontrola MeSH
- stilbeny farmakologie MeSH
- synthasa oxidu dusnatého, typ II genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- experimenty na zvířatech MeSH
- financování organizované MeSH
- galaktosamin farmakologie toxicita MeSH
- hepatocyty metabolismus účinky léků MeSH
- játra metabolismus účinky léků zranění MeSH
- krysa rodu rattus MeSH
- stilbeny farmakologie MeSH
- techniky tkáňových kultur využití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- abstrakty MeSH
