Robust Chiral Organization of Cellulose Nanocrystals in Capillary Confinement.

We showed large area uniformly aligned chiral photonic bioderived films from a liquid crystal phase formed by a cellulose nanocrystal (CNC) suspension placed in a thin capillary. As a result of the spatial confinement of the drying process, the interface between coexisting isotropic and chiral phases aligns perpendicular to the long axis of the capillary. This orientation facilitates a fast homogeneous growth of chiral pseudolayers parallel to the interface. Overall, the formation of organized solids takes hours vs weeks in contrast to the slow and heterogeneous process of drying from the traditional dish-cast approach. The saturation of water vapor in one end of the capillary causes anisotropic drying and promotes unidirectional propagation of the anisotropic phase in large regions that results in chiral CNC solid films with a uniformly oriented layered morphology. Corresponding ordering processes were monitored in situ at a nanoscale, mesoscale, and microscopic scale with complementary scattering and microscopic techniques. The resulting films show high orientation order at a multilength scale over large regions and preserved chiral handedness causing a narrower optical reflectance band and uniform birefringence over macroscopic regions in contrast to traditional dish-cast CNC films and those assembled in a magnetic field and on porous substrates. These thin films with a controllable and well-identified uniform morphology, structural colors, and handedness open up interesting possibilities for broad applications in bioderived photonic nanomaterials.

New Ceratocystis species associated with rapid death of Metrosideros polymorpha in Hawai'i.

The native 'ohi'a lehua (Metrosideros polymorpha) has cultural, biological and ecological significance to Hawai'i, but it is seriously threatened by a disease commonly referred to as rapid 'ohi'a death (ROD). Preliminary investigations showed that a Ceratocystis species similar to C. fimbriata s.lat. was the cause of the disease. In this study, we used a combination of the phylogenetic, morphological and biological species concepts, as well as pathogenicity tests and microsatellite analyses, to characterise isolates collected from diseased 'ohi'a trees across Hawai'i Island. Two distinct lineages, representing new species of Ceratocystis, were evident based on multigene phylogenetic analyses. These are described here as C. lukuohia and C. huliohia. Ceratocystis lukuohia forms part of the Latin American clade (LAC) and was most closely associated with isolates from Syngonium and Xanthosoma from the Caribbean and elsewhere, including Hawai'i, and C. platani, which is native to eastern USA. Ceratocystis huliohia resides in the Asian-Australian clade (AAC) and is most closely related to C. uchidae, C. changhui and C. cercfabiensis, which are thought to be native to Asia. Morphology and interfertility tests support the delineation of these two new species and pathogenicity tests show that both species are aggressive pathogens on seedlings of M. polymorpha. Characterisation of isolates using microsatellite markers suggest that both species are clonal and likely represent recently-introduced strains. Intensive research is underway to develop rapid screening protocols for early detection of the pathogens and management strategies in an attempt to prevent the spread of the pathogens to the other islands of Hawai'i, which are currently disease free.

Small-angle neutron scattering study of a dense microemulsion system formed with an ionic liquid.

Mixtures of water, octane and 1-octanol with 1-tetradecyl-3-methylimidazolium chloride (C14MIM·Cl), often referred to as a surface active ionic liquid (SAIL), form water-in-oil microemulsions that have potential application as extraction media for various metal ions. Here, we present a structural study by small-angle neutron scattering (SANS) of dense microemulsions formed by surfactant-rich mixtures of these four compounds to understand how the SAIL can be used to tune the structures and properties of the microemulsions. The SANS experiments revealed that the microemulsions formed are composed of two phases, a water-in-oil microemulsion and a bicontinuous microemulsion, which becomes the dominant phase at high surfactant concentration. In this concentration regime, the surfactant film becomes more rigid, having a higher bending modulus that results from the parallel stacking of the imidazolium ring of the SAIL. At lower surfactant concentrations, the molecular packing of the SAIL does not change with the water content of the microemulsion. The results presented here correlate well with previously observed changes in the interaction between the IL cation and metal ions (Y. Tong, L. Han and Y. Yang, Ind. Eng. Chem. Res., 2012, 51, 16438-16443), while the capacity of the microemulsion system for water remains high enough for using the system as an extraction medium.

Aspects of the design protocol and the statistical methods for analysis of tar, nicotine and carbon monoxide yields in cigarette smoke that can affect the measurement variability within collaborative studies.

Statistical principles described in ISO 5725-1 (1994) are a robust basis for evaluating cigarette smoke data from collaborative studies under the ISO 3308 machine smoking and for specifying the criteria for the removal of outlier data and determination of mean yields and their variability. However, the standard only provides recommendations on outlier removal that should be taken into account by experts who undertake data interpretation. The potential for over-interpretation of data from small numbers of laboratories is highlighted and recommendations made to deal with this possibility. Key variables to the statistical analysis, the number of cigarettes per replicate and replicates performed in each laboratory, the number of participating laboratories and the use of linear and rotary smoking machines in smoke collection, are identified and their relevance to obtaining robust data are considered. The statistical methods routinely used for data analysis from the ISO regime, are re-assessed for their suitability to analyse data obtained under the Canadian intense (CI) regime, where yield differences between linear and rotary smoking machines are found. This machine effect can lead to more outliers being detected and difficulties in outlier detection which may affect the provision of robust estimates of mean yields, repeatability and reproducibility.

Lithium blocks a phosphoinositide-mediated cholinergic response in hippocampal slices.

The effects of lithium on inositol phosphate metabolism may account for the therapeutic actions of lithium in affective disorder. Muscarinic stimulation of the phosphoinositide system blocks synaptic inhibitory actions of adenosine in the hippocampal slice. At therapeutic concentrations, lithium diminished this muscarinic response, whereas rubidium, which does not affect phosphoinositide metabolism, had no effect. A dampening of phosphoinositide-mediated neurotransmission may explain the normalizing effects of lithium in treating both mania and depression.

A dynamical model of environmental effects on allocation to carbon-based secondary compounds in juvenile trees.

BACKGROUND AND AIMS: Patterns and variations in concentration of carbon-based secondary compounds in plant tissues have been explained by means of different complementary and, in some cases, contradictory plant defence hypotheses for more than 20 years. These hypotheses are conceptual models which consider environmental impacts on plant internal demands. In the present study, a mathematical model is presented, which converts and integrates the concepts of the 'Growth-Differentiation Balance' hypothesis and the 'Protein Competition' model into a dynamic plant growth model, that was tested with concentration data of polyphenols in leaves of juvenile apple, beech and spruce trees. The modelling approach is part of the plant growth model PLATHO that considers simultaneously different environmental impacts on the most important physiological processes of plants. METHODS: The modelling approach for plant internal resource allocation is based on a priority scheme assuming that growth processes have priority over allocation to secondary compounds and that growth-related metabolism is more strongly affected by nitrogen deficiency than defence-related secondary metabolism. KEY RESULTS: It is shown that the model can reproduce the effect of nitrogen fertilization on allocation patterns in apple trees and the effects of elevated CO(2) and competition in juvenile beech and spruce trees. The analysis of model behaviour reveals that large fluctuations in plant internal availability of carbon and nitrogen are possible within a single vegetation period. Furthermore, the model displays a non-linear allocation behaviour to carbon-based secondary compounds. CONCLUSIONS: The simulation results corroborate the underlying assumptions of the presented modelling approach for resource partitioning between growth-related primary metabolism and defence-related secondary metabolism. Thus, the dynamical modelling approach, which considers variable source and sink strengths of plant internal resources within different phenological growth stages, presents a successful translation of existing concepts into a dynamic mathematical model.

New sources and instrumentation for neutrons in biology.

Neutron radiation offers significant advantages for the study of biological molecular structure and dynamics. A broad and significant effort towards instrumental and methodological development to facilitate biology experiments at neutron sources worldwide is reviewed.

Neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide chemotherapy followed by docetaxel in refractory patients with locally advanced breast cancer.

The objective of this study was to evaluate the clinical response of locally advanced breast cancer (LABC) to neoadjuvant (NA) chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and to study the role of docetaxel in patients who fail to respond to first-line chemotherapy. Patients were enrolled who had primary tumours without distant metastasis that were too extensive for conservative surgery. All underwent NA chemotherapy for breast cancer and thereafter surgery and/or radical radiotherapy. NA chemotherapy with FEC was administered to 88 patients between February 1998 and June 2005. A median of 6 cycles of FEC (range 1-8) was given, followed in 21 cases by a median of 4 cycles (range 2-6) of docetaxel. Where clinically established, with FEC the clinical complete response (cCR) was 22/81 (27%), clinical partial response (cPR) 41/81 (51%), clinical stable disease (cSD) 18/81 (22%). In patients where the response to FEC was regarded as insufficient, docetaxel was given. Response rates were cCR 3/21 (14%); cPR 10/21 (48%), cSD 8/21 (38%). There were 11 cases of pathological complete response (pCR), 9 in the FEC-only group and 2 in the docetaxel group. Following chemotherapy 49 (56%) patients underwent mastectomy, 32 (36%) breast conserving surgery and 5 (6%) radical radiotherapy, giving a breast conservation rate of 42%. Two patients died before receiving surgery or radical radiotherapy. The results show that neoadjuvant FEC is a reasonable NA therapy in breast cancer and that docetaxel is effective in FEC refractory cases. Only 8 of 81 (10%) assessable patients did not respond to any chemotherapy, giving an overall clinical response rate of 90%, which is comparable to studies in which taxanes were given irrespective of response to preceding therapy with antracycline including regimes.

Modification of primary and secondary metabolism of potato plants by nitrogen application differentially affects resistance to Phytophthora infestans and Alternaria solani.

Potato plants ( SOLANUM TUBEROSUM L. cv. Indira) were grown at two levels of N supply in the greenhouse. Plants supplied with 0.8 g N per plant (high N variant) showed significantly increased biomass as compared to plants without additional N fertilisation (low N variant). C/N ratio was lower and protein content was higher in leaves of the high N variant. The concentration of chlorogenic acids and flavonols was significantly lower in leaves from the high N variant. Whereas resistance to ALTERNARIA SOLANI increased when plants were supplied with additional nitrogen, these plants were more susceptible to PHYTOPHTHORA INFESTANS. After infection with both pathogens, we found a strong induction of p-coumaroylnoradrenaline and p-coumaroyloctopamine, which are identified for the first time in potato leaves and are discussed as resistance factors of other solanaceous plants.

Endothelial tissue-type plasminogen activator release in coronary heart disease: Transient reduction in endothelial fibrinolytic reserve in patients with unstable angina pectoris or acute myocardial infarction.

OBJECTIVES: We sought to examine whether the disturbed fibrinolytic system in patients with an acute coronary syndrome is associated with a reduced endothelial fibrinolytic capacity. BACKGROUND: Intracoronary thrombus formation is a frequent finding in acute coronary syndromes. Systemic alterations of coagulation and fibrinolysis are known to occur, but possible disturbances of endothelial fibrinolytic function have not been investigated. METHODS: We compared 42 patients with an acute coronary syndrome (acute myocardial infarction in 11 and unstable angina pectoris in 31) with 25 patients with stable angina. Venous blood was sampled serially for determination of markers of the fibrinolytic system and of hypercoagulability from admission to day 10. An occlusion test to determine the maximal endothelial tissue-type plasminogen activator (t-PA) release was also performed. RESULTS: Both on day 0 and day 10, patients with an acute coronary syndrome had a marked elevation of t-PA mass concentration (mean value +/- SEM 14.4 +/- 1.6 [day 0], 18.9 +/- 2.5 ng/ml [day 10]) and of plasminogen activator inhibitor (PAI) (9.4 +/- 2.2 [day 0], 11.3 +/- 2.6 AU/liter [day 10], p < 0.05 vs. patients with stable angina). There was also a hypercoagulative state with elevated thrombin activity and increased D-dimers (p < 0.05 vs. patients with stable angina). Maximal endothelial t-PA release was initially reduced (p < 0.05 vs. patients with stable angina) to 2.3 +/- 0.9 ng/ml, but levels recovered during follow-up to 4.4 +/- 1.4 ng/ml (vs. 5.7 +/- 1.5 ng/ml in patients with stable angina). CONCLUSIONS: Despite the known prolonged systemic alteration of fibrinolysis in acute coronary syndromes, endothelial fibrinolytic capacity is reduced only during the acute phase and becomes normalized during follow-up, and thus is linked more to intravascular thrombus formation than to steady state levels of markers of the fibrinolytic system.

Biochemical Plant Responses to Ozone (IV. Cross-Induction of Defensive Pathways in Parsley (Petroselinum crispum L.) Plants).

Parsley (Petroselinum crispum L.) is known to respond to ultraviolet irradiation by the synthesis of flavone glycosides, whereas fungal or elicitor stress leads to the synthesis of furanocoumarin phytoalexins. We tested how these defensive pathways are affected by a single ozone treatment (200 nL L-1; 10 h). Assays were performed at the levels of transcripts, for enzyme activities, and for secondary products. The most rapid transcript accumulation was maximal at 3 h, whereas flavone glycosides and furanocoumarins were maximally induced at 12 and 24 h, respectively, after the start of ozone treatment. Ozone acted as a cross-inducer because the two distinct pathways were simultaneously induced. These results are consistent with the previously observed ozone induction of fungal and viral defense reactions in tobacco, spruce, and pine.

Growth parameters and resistance against Drechslera teres of spring barley (Hordeum vulgare L. cv. Scarlett) grown at elevated ozone and carbon dioxide concentrations.

Spring barley ( Hordeum vulgare L. cv. Scarlett) was grown at two CO2 levels (400 vs. 700 ppm) combined with two ozone regimes (ambient vs. double ambient) in climate chambers for four weeks, beginning at seedling emergence. Elevated CO2 concentration significantly increased aboveground biomass, root biomass, and tiller number, whereas double ambient ozone significantly decreased these parameters. These ozone-induced reductions in growth parameters were strongly overridden by 700 ppm CO2. The elevated CO2 level increased C : N ratio of the leaf tissue and leaf starch content but decreased leaf protein levels. Exposure to double ambient ozone did not affect protein content and C : N ratio but dramatically increased leaf starch levels at 700 ppm CO2. Resistance against Drechslera teres (Sacc.) Shoemaker was increased in leaves grown at double ambient ozone but was less obvious at 700 ppm than at 400 ppm CO2. Constitutive activities of beta-1,3-glucanase and chitinase were significantly higher in leaves grown at double ambient ozone compared to ambient ozone levels. The sum of methanol-soluble and alkali-released cell wall-bound aromatic metabolites (i.e., C-glycosylflavones and several structurally unidentified metabolites) and lignin contents did not show any treatment-dependent differences.

Short term effects of ozone on the plant-rhizosphere-bulk soil system of young beech trees.

Plant growth largely depends on microbial community structure and function in the rhizosphere. In turn, microbial communities in the rhizosphere rely on carbohydrates provided by the host plant. This paper presents the first study on ozone effects in the plant-rhizosphere-bulk soil system of 4-year-old beech trees using outdoor lysimeters as a research platform. The lysimeters were filled with homogenized soil from the corresponding horizons of a forest site, thus minimizing field heterogeneity. Four lysimeters were treated with ambient ozone (1 x O3) and four with double ambient ozone concentrations (2 x O3; restricted to 150 ppb). In contrast to senescence, which was almost unaffected by ozone treatment, both the photochemical quantum yield of photosystem II (PSII) and leaf gas exchange were reduced (11 - 45 %) under the elevated O3 regime. However, due to large variation between the plants, no statistically significant O3 effect was found. Even though the amount of primary metabolites, such as sugar and starch, was not influenced by elevated O3 concentrations, the reduced photosynthetic performance was reflected in leaf biochemistry in the form of a reduction in soluble phenolic metabolites. The rhizosphere microbial community also responded to the O3 treatment. Both community structure and function were affected, with a tendency towards a lower diversity and a significant reduction in the potential nutrient turnover. In contrast, litter degradation was unaffected by the fumigation, indicating that in situ microbial functionality of the bulk soil did not change.

Beech leaf colonization by the endophyte Apiognomonia errabunda dramatically depends on light exposure and climatic conditions.

Ozone and light effects on endophytic colonization by Apiognomonia errabunda of adult beech trees (Fagus sylvatica) and their putative mediation by internal defence compounds were studied at the Kranzberg Forest free-air ozone fumigation site. A. errabunda colonization was quantified by "real-time PCR" (QPCR). A. errabunda-specific primers allowed detection without interference by DNA from European beech and several species of common genera of plant pathogenic fungi, such as Mycosphaerella, Alternaria, Botrytis, and Fusarium. Colonization levels of sun and shade leaves of European beech trees exposed either to ambient or twice ambient ozone regimes were determined. Colonization was significantly higher in shade compared to sun leaves. Ozone exhibited a marginally inhibitory effect on fungal colonization only in young leaves in 2002. The hot and dry summer of 2003 reduced fungal colonization dramatically, being more pronounced than ozone treatment or sun exposure. Levels of soluble and cell wall-bound phenolic compounds were approximately twice as high in sun than in shade leaves. Acylated flavonol 3- O-glycosides with putatively high UV-B shielding effect were very low in shade canopy leaves. Ozone had only a minor influence on secondary metabolites in sun leaves. It slightly increased kaempferol 3- O-glucoside levels exclusively in shade leaves. The frequently prominent hydroxycinnamic acid derivative, chlorogenic acid, was tested for its growth inhibiting activity against Apiognomonia and showed an IC50 of approximately 8 mM. Appearance of Apiognomonia-related necroses strongly correlated with the occurrence of the stress metabolite, 3,3',4,4'-tetramethoxybiphenyl. Infection success of Apiognomonia was highly dependent on light exposure, presumably affected by the endogenous levels of constitutive phenolic compounds. Ozone exerted only minor modulating effects, whereas climatic factors, such as pronounced heat periods and drought, were dramatically overriding.

Supramolecular structures of peptide assemblies in membranes by neutron off-plane scattering: method of analysis.

In a previous paper (Yang et al., Biophys. J. 75:641-645, 1998), we showed a simple, efficient method of recording the diffraction patterns of supramolecular peptide assemblies in membranes where the samples were prepared in the form of oriented multilayers. Here we develop a method of analysis based on the diffraction theory of two-dimensional liquids. Gramicidin was used as a prototype model because its pore structure in membrane in known. At full hydration, the diffraction patterns of alamethicin and magainin are similar to gramicidin except in the scale of q (the momentum transfer of scattering), clearly indicating that both alamethicin and magainin form pores in membranes but of different sizes. When the hydration of the multilayer samples was decreased while the bilayers were still fluid, the in-plane positions of the membrane pores became correlated from one bilayer to the next. We believe that this is a new manifestation of the hydration force. The effect is most prominent in magainin patterns, which are used to demonstrate the method of analysis. When magainin samples were further dehydrated or cooled, the liquid-like diffraction turned into crystal-like patterns. This discovery points to the possibility of investigating the supramolecular structures with high-order diffraction.

Correlation between coronary morphology and molecular markers of fibrinolysis in unstable angina pectoris.

BACKGROUND: In acute coronary syndromes, marked alterations of coagulation and fibrinolysis have been observed, but no data are available concerning a possible relation to coronary stenosis morphology. METHODS: Thirty one patients with unstable angina pectoris were included. Culprit stenosis morphology judged from coronary angiography was graded using the modified ACC/AHA classification. Molecular and functional markers of hemostasis and fibrinolysis were determined from venous plasma samples obtained at admission. RESULTS: Patients with unstable angina pectoris had a moderate procoagulant state, especially a contact phase activation compared with age-matched controls (factor XII 93.9 +/- 5.6 vs 112.8 +/- 5.4%; P < 0.05; high molecular weight kininogen 55.3 +/- 5.4 vs 86.1 +/- 6.5%; P < 0.01). Thrombin-antithrombin (TAT) was not significantly elevated (7.6 +/- 1.9 vs 4.0 +/- 0.5 microg/l). Elevated plasminogen activator mass concentration (16.6 +/- 2.1 vs 5.4 +/- 0.6 ng/ml; P < 0.01) and plasminogen activator inhibitor (PAI) activity (9.9 +/- 3.0 vs 5.6 +/- 3.0 AU/ml; P < 0.05) indicated an alteration of the fibrinolysis. Complexity of coronary stenosis was positively correlated with tissue-type plasminogen activator (TPA) mass concentration (P < 0.01) and PAI activity (P < 0.05). No association was found to markers of a hypercoagulative state. CONCLUSION: These findings indicate a relation between alterations of the fibrinolytic system and coronary morphology, whereas the acute changes of coagulation occur independently of culprit stenosis complexity.

Activation markers of coagulation and fibrinolysis: alterations and predictive value in acute coronary syndromes.

Several alterations of the coagulation, of the fibrinolysis and of inflammation are known in patients with acute coronary syndromes. To extent current knowledge of the pathophysiology and to optimize therapeutical strategies, the new molecular markers can be used in clinical studies. Furthermore, several studies were undertaken to assess the prognostic value of activation markers of these systems for patients with unstable angina pectoris and acute myocardial infarction with or without thrombolytic therapy. The majority of studies focussed on markers of thrombin activation, fibrinogen, fibrin degradation products and t-PA and its main inhibitor PAI-1. While there are stimulating results from larger studies, the value for prognosis for the individual patient still is limited by the overlap of patients with good versus a poor outcome.

Fibrin specificity and procoagulant effect related to the kallikrein-contact phase system and to plasmin generation with double-bolus reteplase and front-loaded alteplase thrombolysis in acute myocardial infarction.

This study was undertaken to compare the effects of reteplase and alteplase regimens on hemostasis and fibrinolysis in acute myocardial infarction (AMI). Thrombolytic treatment in patients with AMI is hampered by paradoxical procoagulant effects that favor early reocclusion. In vivo data comparing this effect and the fibrin specificity of double-bolus reteplase and front-loaded alteplase regimens are not available. In a prospective, randomized study, 50 patients with AMI were either treated with double bolus (10 + 10 U) reteplase or with front-loaded alteplase (up to 100 mg) within 6 hours of symptom onset. Thirty apparently healthy persons served as controls. Molecular markers of coagulation and fibrinolysis were serially examined for up to 5 days. Paradoxical thrombin activation at 3 hours after initiation of therapy was comparable between reteplase and alteplase. Reteplase (65 +/- 5 U/L) and alteplase (72 +/- 8 U/L) caused significantly elevated kallikrein activity at 3 hours after adminstration (p <0.01 vs controls 30 +/- 1 U/L). Fibrin specificity was less for reteplase (p <0.05) with a decrease in fibrinogen at 3 hours to 122 +/- 27 mg/dl versus 224 +/- 28 mg/dl for alteplase (p <0.01 and p <0.05 vs controls). D-Dimer levels at 3 hours were higher (p <0.05) after reteplase (5,459 +/- 611 ng/ml) versus alteplase (3,445 +/- 679 ng/ml) (both p <0.01 vs controls 243 +/- 17 ng/ml). Plasmin generation (plasmin-antiplasmin complexes) was significantly (p <0.01) increased at 3 hours with both regimens to 27,079 +/- 3,964 microg/L (reteplase) and 19,522 +/- 2,381 microg/L (alteplase). The data from 3 hours after start of thrombolytic therapy proved less marked fibrin specificity of the reteplase regimen (in vivo) compared with front-loaded alteplase. Both regimens have a moderate procoagulant effect without differences in activation of the kallikrein system.

Misclassification of smoking in a follow-up population study in southern Germany.

Smoking prevalence in southern Germany was studied in 1984-1985 using a representative cohort of 4022 subjects aged 25 to 64 years, with 3753 reinterviewed in 1987-1988. Data were available for analysis from interviews on self-reported smoking behavior and from serum cotinine measurements in both investigations. More men than women reported current smoking, and particularly heavy smoking. Serum cotinine levels increased steadily with the daily number and nicotine yield of cigarettes smoked. Mean cotinine levels in ex-smokers were higher than those in never smokers, suggesting that a higher percentage of current smokers are misclassified as ex-smokers than never smokers. Using cotinine rather than self-reported smoking data increased the proportion of true smokers in the subgroup of self-reported smokers by about 3% in males and by about 1% in females. Data from the reinterviews revealed that reported smoking status confirmed by cotinine measurement in 1987-1988 conflicted in a number of cases with the data obtained in 1984-1985 using the same procedure. For example, 0.1% of those who stated they were current regular smokers, 4.3% of those who stated they were current occasional smokers, and 17.6% of those who stated they were ex-smokers in 1984-1985 claimed in 1987-1988 to have never smoked. This misclassification of ex-smokers was higher in women. Altogether the true proportion of ex-smokers among self-reported never smokers was about 9.7% (17.8% in men and 6.7% in women). The widely variable uptake of tobacco smoke by smokers, as well as the misclassification of true smokers and ex-smokers as never smokers, needs to be considered in epidemiological studies evaluating the health risks from both active and passive smoking.

Lower cardiac troponin T levels in patients undergoing cardiopulmonary bypass and receiving high-dose aprotinin therapy indicate reduction of perioperative myocardial damage.

Nowadays in many European heart centers the activation of the fibrinolytic system, always occurring during cardiopulmonary bypass, is routinely reduced by high-dose application of the proteinase inhibitor aprotinin (total of > 4 million KIU). In this study parameters of myocardial ischemic injury were investigated with the aim of identifying further benefits of aprotinin, particularly the protection of the myocardium during the ischemic period of aortic crossclamping. Forty patients with coronary artery disease who underwent aorta-coronary bypass grafting were randomly and in a double-blind fashion divided into two groups, one that received high-dose aprotinin therapy and one that received only saline solution. Markers such as troponin T, with high specificity for detection of myocardial ischemia and infarction, and markers with more general specificity such as creatine kinase, its isoenzyme, and lactate dehydrogenase showed significantly increased values after ischemia in both groups. In patients who received high-dose aprotinin therapy 3 days after cardiopulmonary bypass all parameters measured showed significantly lower levels compared with those in the control group. Therefore we can presume that the application of high-dose aprotinin provides myocardial protection from perioperative ischemic injury.