Pollen-based quantitative reconstructions of Holocene regional vegetation cover (plant-functional types and land-cover types) in Europe suitable for climate modelling.

We present quantitative reconstructions of regional vegetation cover in north-western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1° × 1° spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. The REVEALS model was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant-functional types and three land-cover types [evergreen trees, summer-green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6k bp and modern time in the REVEALS estimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2k bp is significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer-green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or as REVEALS estimates of tree cover. For instance, when Pinus is dominant over Picea as pollen percentages, Picea is dominant over Pinus as REVEALS estimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover-climate interactions, biodiversity and human resources.

Actual position of interleukin(IL)-33 in atherosclerosis and heart failure: Great Expectations or En attendant Godot?

Atherosclerosis has been recognized as an inflammatory/autoimmune disease. The long-standing low-grade inflammation which fuels its development is primarily focused on the components of the vessel wall. Originally, inflammation in atherogenesis was supposed to be driven by the pro-inflammatory Th1 cellular and cytokine immune response. On the basis of accumulating evidence, this view has been re-evaluated to include the Th17/Th1 axis which is shared by most diseases of sterile inflammation. The anti-inflammatory Th2 cellular and cytokine immune response is initiated concomitantly with the former two, the latter dampening their harmful reactions which culminate in full-blown atherosclerosis. Interleukin-33, a novel member of the IL-1 cytokine superfamily, was suggested to take part in the anti-atherogenic response by mediating the Th1-to-Th2 switch of the immune reactions. However, IL-33 is a multifaceted mediator with both pro- and anti-inflammatory activities, also called a "dual factor" or a "Janus face" interleukin. IL-33 occurs both in an extracellular (cytokine-like) and in a nuclear-bound (transcription factor-like) form, each of them performing distinct activities of their own. This review article presents the latest data relevant to IL-33's role in atherosclerosis and cardiac diseases as perceived by a cardiologist and a cardiac surgeon.

Inhibitory CD200R and proapoptotic CD95/CD95L molecules on innate immunity cells are modulated by cardiac surgery.

INTRODUCTION: Cardiac surgery directly initiates a systemic inflammatory response with the activation of both cellular and humoral parts of the immune system. Exaggerated immune system activation is associated with a risk of life-threatening multi-organ dysfunction (MOD) and increased morbidity and mortality in the postoperative period. The immune system response is regulated and terminated by inhibitory mechanisms, including the regulatory membrane molecules, such as CD200R, CD95, CD95L and soluble sCD200R. METHODS: We measured the expression of CD95, CD95L, CD200R and sCD200R molecules in granulocyte and monocyte populations in blood samples of 30 patients who underwent coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). Samples collected before surgery, after surgery and in the postoperative period were analyzed by flow cytometry and ELISA. RESULTS: We found a significant increase in the percentage of granulocytes featuring the anti-inflammatory molecule CD200R (from 5% to 17.8%) after surgery. We presume that these cells were less susceptible to apoptosis because they rarely expressed CD95 as the CD200R(+)CD95(-) granulocyte sub-population prevailed. Only a small percentage of CD200R(+) granulocytes expressed simultaneously CD95 (from 0.5 to 2.06 %). This small population of CD200R(+)CD95(+) cells decreased expression of CD200R after surgery and, thus, was likely to be a source of increased sCD200R in serum (from 96 to 294 ng/mL). Also, the expression of CD95L on CD200R(+) granulocytes and CD95 on CD200R(+) monocytes was affected by surgery. The percentage of CD200R(+) monocytes was elevated on the 1(st) postoperative day (from 30.6 to 49.4 %) and dropped below the preoperative value on the 7(th) day after surgery (from 30.6 to 19.8 %). This population comprised mainly CD200R(+)CD95(+) monocytes in which the enhanced expression of CD95 was found. CONCLUSION: Our data show that the expression of CD200R, CD95 and CD95L was influenced by cardiac surgery and imply the role of these membrane molecules in cell regulation-inhibition and apoptosis following cardiac surgery.

The long pentraxin PTX3: a candidate anti-inflammatory mediator in cardiac surgery.

Coronary artery bypass grafting (CABG) is performed with the use of cardiopulmonary bypass (CPB) and cardioplegic arrest (CA) of the heart. The advantage of this technique, alternatively referred to as "on-pump" surgery, resides, for the surgeon, in relatively easy access to and manipulation with the non-beating, bloodless heart. However, the advantage that is, thereby, gained by the patient is paid off by an increased susceptibility to postoperative systemic inflammatory response syndrome (SIRS). Under unfavorable conditions, the inflammatory syndrome may develop into life-threatening forms of MODS (multiple organ dysfunction syndrome) or even MOFS (multiple organ failure syndrome). Deliberate avoidance of CPB, also known as "off-pump" surgery, attenuates early postoperative inflammation throughout its trajectory of SIRS→MODS→MOFS, but, in the long run, there appears to be no substantial difference in the overall mortality rates. In the last years, our knowledge of the pathophysiology of surgical inflammation has increased considerably. Recent findings, highlighting the as yet rather obscure role of pentraxin 3 (PTX3) in these processes, are discussed in this review article.

Pentraxin 3(PTX 3): an endogenous modulator of the inflammatory response.

Inflammatory or anti-inflammatory? That is the question as far as the acute-phase response and its mediators, the pentraxins, are concerned. Only some ten years ago, the classical or short pentraxin C-reactive protein and the newly discovered long pentraxin PTX3 were considered to exert most of the detrimental effects of acute inflammation, whether microbial or sterile in origin. However, accumulating evidence suggests an at least dichotomous, context-dependent outcome attributable to the pentraxins, if not a straightforward anti-inflammatory nature of the acute-phase response. This paper is focused on the inherent effects of pentraxin 3 in inflammatory responses, mainly in coronary artery disease and in Aspergillus fumigatus infection. Both are examples of inflammatory reactions in which PTX3 is substantially involved; the former sterile, the latter infectious in origin. Apart from different inducing noxae, similarities in the pathogenesis of the two are striking. All the same, the introductory question still persists: is the ultimate impact of PTX3 in these conditions inflammatory or anti-inflammatory, paradoxical as the latter might appear? We try to provide an answer such as it emerges in the light of recent findings.

Interferon gamma receptor expression on granulocytes of cardiac surgical patients is modulated differently by the type of cardiopulmonary bypass used.

AIMS: To follow the IFNγ receptor expression on monocytes and granulocytes of cardiac surgical patients with respect to the type of cardiopulmonary bypass (CPB). METHODS: Expression of IFNγ receptor on monocytes and granulocytes of 26 cardiac surgical patients operated with the use of either "standard" or "miniaturised" CPB was determined by flow cytometry. RESULTS: The significant increase in IFNγ receptor expression on monocytes on the 1(st) and on the 3(rd) postoperative days was revealed in both groups of patients (p<0.001) irrespective of the type of CPB used, being non-significantly different between groups. In contrast, the expression of IFNγ on granulocytes displayed significant differences in terms of the CPB used. Whereas, in "standard" CPB patients, granulocyte INFγ receptor expression reached its maximum immediately after surgery (p<0.01), in "miniivasive" CPB patients, the peak in INFγ receptor expression was postponed to the 1(st) postoperative day (p<0.05). Statistically significantly higher IFNγ receptor expression on granulocytes was found in "standard" CPB patients (p<0.05). CONCLUSION: Compared to "miniaturised" CPB patients, the significantly higher IFNγ receptor expression on granulocytes was found in "standard" CPB patients (p<0.05) on the 1(st) postoperative day.

Impact of methylprednisolone in priming solution of cardiopulmonary bypass on anti-inflammatory CD163 receptor during cardiac surgery.

We evaluated the influence of methylprednisolone in cardiopulmonary bypass fluid on scavenger receptor for hemoglobin CD163 molecule expression on monocytes of patients who underwent elective coronary artery bypass grafting with cardiopulmonary bypass with either exposure to methylprednisolone present in the cardiopulmonary bypass fluid (20 patients), or without methylprednisolone in the cardiopulmonary bypass fluid (22 patients) and operated on without cardiopulmonary bypass (42 patients). The dynamics of CD163 expression was also followed in patients operated on without cardiopulmonary bypass. This study was a retrospective analysis of a comparison of two studies. The expression of CD163 was determined quantitatively by standardized flow cytometry technique. The similarities in the dynamics of CD163 monocyte expression, comparing the patients operated on with or without cardiopulmonary bypass, were found. Compared to the preoperative level, CD163 monocyte expression was significantly elevated on the 1(st) postoperative day. Monocyte CD163 expression on the 1(st) postoperative day was evidently similar in both groups of patients operated without cardiopulmonary bypass (median value of mean fluorescence intensity (MFI) 18,896; interquartile range from 27,538 to 57,711; median value of MFI 18,863; interquartile range from 16,514 to 26,559; n.s.), suggesting high reproducibility of our flow cytometric method; the monocyte CD163 expression was significantly higher (median value of MFI 37,902; interquartile range from 27,538 to 57,711) on the 1(st) postoperative day in patients exposed to methylprednisolone compared to patients without this exposure (median value of MFI 20,995; interquartile range from 16,321 to 29,623) (p<0.001). We concluded that the expression of hemoglobin scavenger receptor CD163 on monocytes of cardiac surgical patients is induced by methylprednisolone present in cardiopulmonary bypass fluid.

Interleukin-33, a novel member of the IL-1/IL-18 cytokine family, in cardiology and cardiac surgery.

Interleukin-33 is a newly recognized cytokine of the IL-1 family. Unlike its other members IL-1α, IL-1ß and IL-18, interleukin-33 induces predominantly Th2-skewed immune responses. In this context, the effects of IL-33 are mostly anti-inflammatory. However, depending on the actual cytokine and cellular milieu, IL-33 can promote both Th1 and Th2 immune reactions. Most importantly for cardiology and cardiac surgery, IL-33 has emerged to represent the as yet unknown ligand of the orphan receptor ST2. Before the advent of IL-33, the ST2 receptor, currently recognized as the soluble one of its two isoforms, was considered to be an unfavorable prognostic marker in myocardial infarction, congestive heart failure and trauma/sepsis shock patients. Now we know that IL-33, when bound to the cellular membrane-anchored ST2L isoform of the receptor, can have certain beneficial effects on the aforementioned conditions. Various forms of IL-33 interaction with the respective isoforms of its cognate receptor are discussed here. The focus is on physiological and prognostic values in cardiac patients.

[Transcription factor Egr-1 in cardiovascular biology]. / Transkripcní faktor Egr-1 v kardiovaskuláirni biologii.

The zinc finger transcription factor Egr-l plays an important role in cardiovascular biology. While binding complementary motifs on DNA in the target genes, Egr-1 either increases or decreases proteosynthesis of many proinflammatory and antiinflammatory mediators. In physiologic circumstances, these mediators support healing and regeneration of damaged tissue, mainly by conducting angioneogenesis. In pathologic circumstances these same mediators take an active part in promoting tissue injury. The participation of the transcription factor Egr-1 in the pathogenesis of atherosclerosis can be traced from the initial phases with the generation of foam cells as far as the onset of acute cardiovascular or cerebrovascular ischemic events. At the same time, transcription factor Egr-1 presents a would-be linker at the level of which converge many seemingly heterogenous atherogenic risk factors such as hyperlipidemic disorders, untoward rheologic changes of blood flow often encountered in arterial hypertension or various infectious agents, with Chlamydia pneumoniae belonging to the most deeply investigated ones. Protective effects of the known anti-atherogenic factors, such as the endogenous antiinflammatory cytokine interleukin-10 or the "pleiotropic" effects of statins can be, at least in part, explained by their inhibitory influence on the activities of the transcription factor Egr-1.

[Transcription factor KLF2 (Krüppel-like factor 2) and natural defence of vascular endothelium]. / Transkripcní faktor KLF2 (Krüppel-like factor 2) a prirozená ochrana cévního endotelu.

Vascular endothelium, monocytes and T-lymphocytes belong to the key cellular populations, which take an active part in the host's defence reactions. A successful course of these reactions is determined by a meticulous control of all phases since the very first steps until final healing of all incurred wounds. Any failure of the control mechanisms may lead to the development of chronic inflammatory diseases with an autoimmune component, such as the rheumatoid arthritis or atherosclerosis. An inflammatory reaction which is already under way is regulated by anti-inflammatory cytokines. However, of equal importance is the maintenance of cellular participants of inflammatory reactions in a quiescent state while no pro-inflammatory stimuli are present. One of the most important endogenous mediators, which prevent a self-initiated activation of endothelial cells, monocytes and T-lymphocytes, is represented by the transcription factor Krüppel-like factor 2. Its impact on the mentioned cells is almost identical with the so-called pleiotropic effects of inhibitors of the enzyme HMG CoA reductase or statins. This review article offers an insight into basic preventive mechanisms exerted by KLF2, notably those related to atherosclerosis.

[Cardiac surgery operations and their influence on serum level of antiinflammatory cytokine interleukin-10]. / Kardiochirurgické operace a jejich vliv na sérovou hladinu protizánetového cytokinu interleukinu-10.

BACKGROUND: Cardiac surgical operation is followed by the development of inflammatory reaction. This reaction is regulated in many ways including the production of antiinflammatory cytokines such as IL-10 to avoid potentially harmful effects of inflammation. METHODS AND RESULTS: We compared serum levels of cytokines IL-10, IL-6, and IL-13 in the group of patients undergoing cardiac surgical operation using either cardiopulmonary bypass (CPB, n=17) or surged on the beating heart (n=17). We found significant elevation in the serum level of IL-10 during surgery with the peak immediately after finishing surgery in CPB patients and at the first postoperative day in non-CPB patients, respectively. There is statistically significantly higher level of IL-10 in CPB patients in comparison with non-CPB patients at the end of surgery. Serum level of IL-6 is elevated in both groups during surgery reaching maximum immediately after surgery in CPB patients and at the first postoperative day in patients without CPB, respectively. The serum levels of IL-13 are only nonsignificantly changed during operation and in postoperative period in both groups. CONCLUSIONS: The intensity of inflammatory response in CPB patients which is enhanced by massive contact activation of blood and extensive ischemia-reperfusion injury is regulated by the production of antiiflammatory IL- 10 cytokine.

[C-reactive protein in the pathogenesis of atherosclerosis: advantage and pitfalls of the "Mainz hypothesis"]. / C-reaktivní protein v patogenezi aterosklerózy: prednosti a úskalí "Mohucské hypotézy"

C-reactive protein can be viewed as a basic marker of activity of the inflammatory response, which modulates the development and the progression of atherosclerosis including its life-threatening complications. At the same time, C-reactive protein represents an active partaker or mediator of this same inflammatory reaction. However, at the very beginning of atherosclerotic disease, C-reactive protein exerts a clear-cut antiatherogenic activity. The two aspects of CRP's function, i.e. both the pro-inflammatory and the anti-inflammatory one, respectively, stem from CRP's extent of co-operation with the complement system. From the evolutional point of view, the anti-inflammatory activity of CRP is the primary one, in that it sets stage for the host to remove foreign particles and to accelerate wound healing. The influence of well-known atherogenic risk factors converts the originally beneficial influence of CRP into pro-inflammatory and pro-atherogenic effects. This review article presents new conclusions from the "Mainz hypothesis". It shows that the primary protective action of CRP resides in its regulatory influence on the extent of activation of the complement system after the latter has been triggered by enzymatically remodeled low-density lipoproteins. In further course of atherosclerotic disease, C-reactive protein exhibits a full-blown proinflammatory activity. It can result in the progression of the primary morphologic lesions up to the development of sudden vascular events.

[The role of pentraxin 3 in the inflammatory and immune response]. / Pentraxin 3 v zánetlivé a imunitní odpovedi.

Pentraxin 3 is the first detected and so far the most important protein from the recently recognized group called the long pentraxins. The structure and function of PTX3 resembles in many aspects that of the short or classical pentraxins, i.e. C-reactive protein and the serum amyloid P component. There are, however, several important differences between the two groups of pentraxins that will be mentioned in more detail in the article. All of the above mentioned pentraxins take an acitve part in the first-line defense of the host against invading pathogenic microorganisms and in the clearance of the host's own apoptotic cells. The latter mechanism impedes the onset of destructive autoimmune reactions. A biologically relevant antipode of PTX3 is represented by TNFalpha. Physiologic course of the defense reactions depends on a closely co-ordinated activity of both peptides. In case of an unchecked or missing activity of either peptide, a disturbance in their mutual balance results in increased susceptibility of the host to conditionally pathogenic fungi or in increased damage to host's own tissues inflicted by the defense reactions. This review article deals with the physiopathologic importace of pentraxin 3 as has been gained on the basis of the most up-to-date information.

[Shared pathogenesis of infectious and cardiovascular diseases--year 2005's view]. / Spolecné patogenetické mechanizmy infekcních a kardiovaskulárních chorob: pohled roku 2005.

Entry of microorganisms into the blood stream provokes a decline in the contractile function of the cardiac muscle. Lipopolysaccharide of Gram-negative bacteria sets off production of pro-inflammatory cytokines including bactericidal concentrations of nitric oxide which set up the first defence line against bacteremia. At the same time, however, the performance of the cardiovascular system is negatively affected. The immediate menace resides in the occurrence of septic shock, while chronic infectious diseases that are accompanied by low-grade inflammation have been suspected to take an active part in the initiation and progression of atherosclerosis. This hypothesis, as attractive as it may appear, has not yet been accepted unequivocally. The article offers an up-to-date review of the signalling cascades which permit activation by lipopolysaccharide of the target cells. The same holds true for cellular activation by non-infectious stimuli. An emerging paradigm seems plausible that the same biologic events which serve to combat acute infection might be in the long run involved in the pathogenesis of atherosclerosis.

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part II: TLR receptors, significance of genetic polymorphism of danger signals receptors]. / Pirrozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy II. cast. Receptory TLR, význam polymorfizmu receptoru pro nebezpecné vzory.

The most important set of receptors for danger patterns are TLR receptors. Together ten different TLR receptors were identified so far. Majority of TLR receptors is expressed on the cell surface to identify extracellulary localized danger signals. Some TLR receptors are also expressed in the intracellular compartment to identify intracellular danger signals. Receptors for danger signals display individual differences delineated by genetic polymorphism. The individual immune reactivity is developed in the context of genetic predisposition and the exposition to variable environmental factors. The differences in an individual immune reactivity are probably responsible for individual susceptibility or resistance to the development of immunopathological reactivity, which is involved in the immunopathogenesis of atherosclerosis.

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part 1: identification of danger signals by innate immunity]. / Prirozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy I. cást: Prirozená imunita, rozlisení signálu nebezpecí.

Cellular and humoral components of innate immunity are able to identify danger signals both of the exogenous and endogenous origin. Exogenous danger signals are evolutionary conserved mosaics of danger patterns which are frequent in pathogenic microbes. Endogenous danger signals are raised during damage of self structures, by oxidative stress and/or by chemical modification of self molecules. Danger signals are identified by several families of molecules which are expressed on the surfaces of innate immunity cells. Among them the TLR receptors family which is associated with intracellular signaling pathway NF-kappaB is one of the most important. The inflammatory response is induced via activated NF-kappaB transcription factor.

Iatrogenic clubbing of the fingers.

We report on a 39-year-old female who had been operated on for an atrial septal defect at the age of 14 years. On operation the inferior vena cava was iatrogenically misdirected into the left atrium. The cyanotic patient, in functional group IV of the NYHA classification, with polyglobulia and clubbing of the fingers was successfully reoperated after 25 years.

Thoracic electrical bioimpedance versus thermodilution in patients post open-heart surgery.

Thoracic electrical bioimpedance cardiography is a non-invasive, continuous and low-cost method of estimation of cardiac output and other haemodynamic parameters. Though subject to continuous technological refinement controversial opinions exist on its validity in subsets of critically ill patients, patients with heart disease or after cardiac surgery. A comparison study between thermodilution (TD) and bioimpedance (TEB) was performed in 28 patients undergoing elective cardiac surgery (CABG, aortic or mitral valve replacement or combined procedures). 128 pairs of cardiac index estimates at specific time points during 20 hours at the postoperative ICU were evaluated. A poor correlation (r = 0.26, p < 0.05, bias -0.07 l.min-1.m2, precision + 1.1 l.min-1.m-2, 95% limits of agreement -2.27-2.13 l.min-1.m-2) between TD and TEB cannot support the routine use of TEB monitoring in early postoperative period after open-heart surgery. Possible reasons of lack of agreement in this population are discussed. Further studies with technically improved bioimpedance cardiographs will be needed.

Morbidity and mortality in patients 70 years of age and over undergoing isolated coronary artery bypass surgery.

BACKGROUND AND AIM: Due to the constantly improving results of surgical revascularization for coronary heart disease even the elderly patients are offered more frequently this type of treatment. Since older age is a harbinger of reduced vital capacity and increased morbidity the results of coronary artery bypass grafting (CABG) in elderly as well as long-term benefit deserve a careful examination. MATERIALS AND METHODS: 1475 isolated CABG procedures performed between 1995 and 1997 in a university hospital cardiac surgery unit, divided in group I (age below 70, n = 1324) and group II (age 70 and over, n = 151). A retrospective analysis of pre-operative, peri-operative and post-operative data. RESULTS: Significant differences (lower BMI and BSA, advanced NYHA and CCS stage, higher prevalence of diabetes, renal dysfunction and extracardial atherosclerotic lesions) were found in elderly. CABG was performed in both groups with no differences in technique of procedure (only slightly longer duration of CPB in group II). However, there was markedly higher mortality (2.3 vs. 7.3%, p < 0.005), incidence of NearMiss+ (18.4 vs. 36.4%, p < 0.005) and post-operative morbidity (34.6 vs. 56.3%, p < 0.005) in the older group, which was also expressed in a longer ICU stay and postoperative hospitalization. CONCLUSION: Coronary revascularization can be performed in elderly with higher but still acceptable risk. Higher mortality and associated morbidity is caused by higher preoperative prevalence of known risk factors as well as generally reduced vital capacity. Surgical procedure should not be denied to elderly population because of the age alone but a careful evaluation of an individual patient is required.

[CD4 lymphopenia and postoperative immunosuppression in cardiac surgery]. / CD4+ lymfopenie a pooperacní imunosuprese v kardiochirurgii.

The diversity and heterogeneity of biologic reactions is a condition sine qua non for the adaptation of live organisms to changes of external environment. Reactions of the immune system enable survival even in extreme conditions. Modern medicine often reaches situations never met by the organism in phylogenesis. Thanks to up-to-date therapeutical approaches many patients survive with grave symptoms such as multiple organ failure and extensive forms of injury. New infectious diseases are emerging, e.g. HIV/AIDS. Notwithstanding the broad array of external insults, it becomes obvious that organisms mobilize defence reactions according to a general scheme. Likewise, exhaustion of the immune potential occurs according to an archetypal pattern. In the case of cell-mediated immunity the faultless course of which is of critical importance for organisms in extreme conditions, the loss begins with the absence of reactivity of T-cells to specific antigens to end with the absence of their reactivity to polyclonal mitogens. The article deals with pathogenic mechanisms underlying the onset of immunodeficiencies caused by both infectious and non-infectious stimuli with special regard being focused on cardiac surgery in extracorporeal circuit.