a1_Modification of low density lipoprotein (LDL) particles due to oxidation, glycation and binding of advanced glycation end-products (AGEs) or malondialdehyde (MDA, a final product of lipid peroxidation) is considered most important in the process of atherogenesis. Oxidatively modified LDL are distinguished by another receptor type, which was discovered on the surface of macrophages and was called the scavenger receptor. Uncontrolled intake of LDL converts macrophages to foam cells; their accumulation under the vascular endothelium is considered as the first stage of atherosclerosis. Oxidation of LDL is a complex process taking place in both the extra- and intracellular space. At the end of this oxidative process, modified LDL particles show chemotactic, cytotoxic and immunogenic properties. Oxidized LDL express a large number of epitopes and cause production of polyclonal autoantibodies against these products, especially against apoB100 modified by MDA and 4-hydroxynonenal. IgoxLDL (antibodies against oxidized LDL) can be demonstrated either directly in intimal lesions or as a component of circulating immune complexes. IgoxLDL do not form a homogeneous group but a varied mixture of antibodies-isoantibodies caused by HDL and LDL polymorphism, antibodies against the lipid phase of LDL and antibodies against modified apoB100 of the immunoglobulin class IgA or IgG. Antibodies against oxLDL were found in many diseases other than atherosclerosis such as diabetes mellitus, renovascular syndrome, uremia, rheumatic fever, morbus Bechtjerev or lupus erythematodes. Newborns have practically the same levels of IgoxLDL as their mothers; however, these values did not differ from those in the healthy population of non-pregnant women of the same age., a2_The decrease in IgoxLDL titer was very slow and lasted many months; that is why this parameter cannot be considered suitable for describing the rapid changes during oxidative stress of the organism. Positive correlation of IgoxLDL with antiphospholipids and other antibodies was repeatedly demonstrated; their determination can thus be used as a marker for the description of total production of autoantibodies in various diseases. The changes and correlations of IgoxLDL, anti-b-2-glycoprotein I IgG and antiphospholipid antibodies support the immunological link between thrombotic and atherosclerotic processes in the human body., A. Steinerová, J. Racek, F. Stožický, T. Zima, L. Fialová, A. Lapin., and Obsahuje bibliografii
a1_Oxidized low density lipoproteins (oxLDL) formed in vivo induce a humoral immune response. Oxidative modification of LDL renders it immunogenic and a heterogeneous population of specific anti-oxLDL antibodies is produced. These antibodies could represent a biological marker of oxidative stress and serve as markers of atherosclerosis. Autoantibodies against oxLDL (oLAb) have been detected in human subjects practically of every age. oLAb also appear in the blood of pregnant women. Some studies have shown that the levels of antibodies to oxLDL were elevated in women with established preeclampsia. The present study was aimed to estimate the oLAb IgG levels in the first and second trimester of pregnancy. Furthermore, we estimated the correlation between maternal serum (MS) levels of oLAb and alpha-1-fetoprotein (MS AFP), human chorionic gonadotrophin (MS HCG) and trophoblast-specific-beta-1-glycoprotein (MS SP1), because these proteins are determined as a part of prenatal biochemical screening for fetal congenital abnormalities. Our study deals with the oLAb changes in women with pregnancy-induced hypertension. We also investigated the correlation between oLAb IgG and anticardiolipin antibodies IgG (ACA) in the serum of pregnant women. We examined 40 pregnant women attending Institute for Mother and Child Care for their antenatal care as outpatients. Routine blood samplings between the 9-13th week of pregnancy and 16-18th week of pregnancy were performed as a part of biochemical prenatal screening for fetal congenital abnormalities (Group 1). Their mean age was 27±4.1 years. Furthermore, we examined 26 women in the second or third trimester with pregnancy-induced hypertension (Group 2). Group 2 was compared with 49 pregnant women in the second or third trimester who were normotensive (Group 3)., a2_We used commercial standardized ELISA kits for determination of oLAb IgG, ACA IgG, MS AFP and MS HCG, MS SP1 was analyzed by single radial immunodiffusion. We did not find any differences in the levels of oLAb IgG in the first and second trimester in the women of Group 1. The correlation between oLAb and ACA IgG was not statistically significant (Spearman coefficient r=0.22, p=0.1). The correlation between oLAb IgG with MS AFP, MS HCG and MS SP1 was not statistically significant. Weak negative correlation for AFP and HCG was suggested both in the first and in the second trimester. The levels of oLAb IgG in the group of women with pregnancy-induced hypertension were significantly lower than in the group of normotensive women (348±388 U/ml v.s. 579±400 mU/ml, p<0.01). We can conclude that the levels of oLAb do not differ in the first and second trimester of gravidity. However, we cannot exclude the possible influence of an inverse relationship between oLAb IgG titers and the synthesis of fetoplacental antigens. This finding is important especially in the context of the results of prenatal biochemical screening. Pregnancy-induced hypertension is associated with lower levels of oLAb. Weak cross-reactivity between oLAb and anticardiolipin antibodies may exist but there is a possibility that there are two different populations of antibodies reacting with various antigens., L. Fialová, L. Mikulíková, I. Malbohan, O. Benešová, S. Štípek, T. Zima, A. Zwinger., and Obsahuje bibliografii
The endothelin axis (endothelins and their receptors) is strongly involved in physiological and pathological processes. ET-1 plays a crucial role in particular in tumor diseases. Endothelin-1 receptors (ETA and ETB) are deregulated and overexpressed in several tumors such as melanoma and glioma. We studied the binding of 24 monoclonal antibodies directed against human ETB receptors (hETB) to different melanoma cell lines. Few of these mAbs bound to all the melanoma cell lines. One of them, rendomab B49, bound to ETB receptors expressed at the surface of human glioma stem cells. More recently, we produced new antibodies directed against human ETA receptor (hETA). Several antibodies have been isolated and have been screened on different tumoral cells lines. As for the mAbs directed against the hETB receptor only some of new antibodies directed against ETA receptor are capable to bind the human tumoral cell lines. Rendomab A63 directed against hETA is one of them. We report the specificity and binding properties of these mAbs and consider their potential use in diagnosis by an in vivo imaging approach., A. Herbet, N. Costa, N. Leventoux, A. Mabondzo, J.-Y. Couraud, A. Borrull, J.-P. Hugnot, D. Boquet., and Seznam literatury
GABA-B receptor agonist SKF97541 exhibits age-dependent anticonvulsant and proconvulsant actions in developing rats. It suppressed tonic phase of generalized seizures induced by pentetrazol in 7-, 12- and 18-day-old rats and increased their latency in 7- and 12-day-old animals. Other results in 18-day-old animals are not so clear. SKF 97541 blocked the appearance of minimal clonic seizures, but tended to decrease latencies of both types of seizures. In addition, it significantly decreases latency of generalized seizures in adult rats. The mixed effects of SKF97541 are in agreement with those of baclofen but there are substantial differences between the actions of these two agonists in individual age groups., P. Mareš., and Obsahuje bibliografii a bibliografické odkazy
It is known that intracellular pathogens interact and react with the cellular immune system through exosomes produced by macrophages. This study aimed to determine whether co-culture of macrophages and Talaromyces marneffei induces exosomes and leads to immune responses. T. marneffei was incubated to collect conidia, co-cultured with human macrophages, which then induced exosomes. In cellular experiments, after extraction and purification, the exosomes were then observed by electron microscopy and detected by flow cytometry and mass spectrometry. In animal experiments, flow cytometry and enzyme-linked immunosorbent assay were used to examine whether exosomes were antigenpresenting. The results showed that purified exosomes produced a pro-inflammatory response and stimulated production of TNF-α in non-fungal-treated macrophages. Protein mass spectrometry analysis of exosomes also indicated their potential ability to activate the internal immune response system and the pro-inflammatory response. Translation and ribosomes were the most abundant GO terms in proteins, and the most relevant KEGG pathway was the biosynthesis of secondary metabolites. Furthermore, in vivo experiments revealed that exosomes induced activation of lymphocytes and increased expression of TNF-α and IL-12 in the lung, mediastinum, and spleen area. In conclusion, exosomes can be released by co-culture of T. marneffei and macrophages, having antigen-presenting functions, promoting macrophage inflammation, and initiating adaptive immune responses. These processes are inextricably linked to the translation of secondary metabolites, ribosomes and biosynthesis.
Uvádíme a porovnáváme názory největších myslitelů antiky a středověku - Platóna, Aristotela, Augustina a Tomáše Akvinského - na povahu a vlastnosti času. Všímáme si, jak se jimi formulované názory a problémy odrážejí v současné fyzice., Pavel Macků, Jan Novotný., and Obsahuje seznam literatury
Microsporidia are a cause of emerging and opportunistic infections in humans and animals. Although two drugs are currently being used to treat microsporidiosis, concerns exist that albendazole is only selective for inhibiting some species of microsporidia that infect mammals, and fumagillin appears to have been found to be toxic. During a limited sequence survey of the Vittaforma corneae (syn. Nosema corneum Shadduck, Meccoli, Davis et Font, 1990) genome, a partial gene encoding for the ParC topoisomerase IV subunit was identified. The purpose of this set of studies was to determine if fluoroquinolones, which target topoisomerase IV, exert activity against Encephalitozoon intestinalis (syn. Septata intestinalis Cali, Kotler et Orenstein, 1993) and V. corneae in vitro, and whether these compounds could prolong survival of V. corneae-infected athymic mice. Fifteen fluoroquinolones were tested. Of these, norfloxacin and ofloxacin inhibited E. intestinalis replication by more than 70% compared with non-treated control cultures, while gatifloxacin, lomefloxacin, moxifloxacin, and nalidixic acid (sodium salt) inhibited both E. intestinalis and V. corneae by at least 60% at concentrations not toxic to the host cells. These drugs were tested in vivo also, where gatifloxacin, lomefloxacin, norfloxacin, and ofloxacin prolonged survival of V. corneae-infected athymic mice (P < 0.05), whereas moxifloxacin and nalidixic acid failed to prolong survival. Therefore, these results support continued studies for evaluating the efficacy of the fluoroquinolones for treating microsporidiosis and for characterizing the target(s) of these fluoroquinolones in the microsporidia.
This study deals with reforms by Josef II, in particular with the abolition of the monasteries as recorded in contemporary sources supporting the reforms being carried out. The author selects some significant themes treated by the proponents of reform. The main theme is the criterion of human nature. Related themes include: monks’ asceticism, celibacy, monasteries as the quintessence of baroque piety, and mendicant orders., Petr Hasan., and Obsahuje bibliografické odkazy
The purpose of this study was to determine the effect of a 15-week omega-3 rich diet on age-related differences in myocardial antioxidant defense and inflammation. 20 mature (M) (6 mo.) and 20 old (O) (15 mo.) male Fisher 344 rats were assigned to two diet groups: Control (CON) or Fish Oil (FO). Following the diet, animals were sacrificed and left ventricular (LV) heart tissue was harvested for biochemical assays and western blot analysis. No differences were observed in expression of LV interleukin-6 (IL-6) and tumor necrosis factor-α as well as hydrogen peroxide (H2O2) production between MCON and OCON. However, LV catalase protein expression and activity were increased in OCON vs. MCON and accompanied by increased expression of superoxide dismutase (SOD)-1. In contrast, LV IL-6 was lower in MFO vs. old rats, and LV H2O2 was decreased in MFO and OFO relative to respective control groups. Protein expression and activity of LV catalase and SOD-1 expression were increased in OFO similarly to OCON, but LV SOD activity was also increased in OFO vs. mature rats. In summary, FO supplementation increased myocardial antioxidant defense in all animals and augmented age-associated increases in antioxidant capacity in the absence of changes in inflammation., S. Lennon-Edwards, T. A. Schellhardt, J. M. Kuczmarski., and Obsahuje bibliografii