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Background: FibroTest (FT) is the most frequently used serum fibrosis marker and consists of an algorithm of five fibrosis markers (alfa2-macroglobulin, apolipoproteinA1, haptoglobin, GGT, bilirubin). The Enhanced Liver Fibrosis (ELF) test consists of an algorithm of three fibrosis markers (hyaluronic acid, amino-terminal propeptide-of-type-III-collagen, tissue-inhibitor of matrix-metaloproteinase-1). While a systematic review has shown comparable results for both individual markers, there has been no direct comparison of both markers. Methods: In the present study, the ELF-test was analyzed retrospectively in patients with chronic liver disease, who received a liver biopsy, transient elastography (TE) and the FibroTest using histology as the reference method. Histology was classified according to METAVIR and the Ludwig's classification (F0-F4) for patients with chronic hepatitis C and B virus (HCV, HBV) infection and primary biliary cirrhosis (PBC), respectively. Results: Seventy-four patients were analysed: 36 with HCV, 10 with HBV, and 28 with PBC. The accuracy (AUROC) for the diagnosis of significant fibrosis (F[greater than or equal to]2) for ELF and FibroTest was 0.78 (95%CI:0.67-0.89) and 0.69 (95%-CI:0.57-0.82), respectively (difference not statistically significant, n.s.). The AUROC for the diagnosis of liver cirrhosis was 0.92 (95%CI:0.83-1,00), and 0.91 (95%CI:0.83-0.99), respectively (n.s.). For 66 patients with reliable TE measurements the AUROC for the diagnosis of significant fibrosis (cirrhosis) for TE, ELF and FT were 0.80 (0.94), 0.76 (0.92), and 0.67 (0.91), respectively (n.s.). Conclusion: FibroTest and ELF can be performed with comparable diagnostic accuracy for the non-invasive staging of liver fibrosis. Serum tests are informative in a higher proportion of patients than transient elastography.
Active chlorine species play a dominant role in the catalytic destruction of stratospheric ozone in the polar vortices during the late winter and early spring seasons. Recently, the correct understanding of the ClO dimer cycle was challenged by the release of new laboratory absorption cross sections (Pope et al., 2007) yielding significant model underestimates of observed ClO and ozone loss (von Hobe et al., 2007). Under this aspect, nocturnal Arctic stratospheric limb emission measurements carried out by the balloon version of the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS-B) from Kiruna (Sweden) on 11 January 2001 and 20/21 March 2003 have been reanalyzed with regard to the chlorine reservoir species ClONO2 and the active species, ClO and ClOOCl (Cl2O2). New laboratory measurements of IR absorption cross sections of ClOOCl for various temperatures and pressures allowed for the first time the retrieval of ClOOCl mixing ratios from remote sensing measurements. High values of active chlorine (ClOx) of roughly 2.3 ppbv at 20 km were observed by MIPAS-B in the cold mid-winter Arctic vortex on 11 January 2001. While nighttime ClOOCl shows enhanced values of nearly 1.1 ppbv at 20 km, ClONO2 mixing ratios are less than 0.1 ppbv at this altitude. In contrast, high ClONO2 mixing ratios of nearly 2.4 ppbv at 20 km have been observed in the late winter Arctic vortex on 20 March 2003. No significant ClOx amounts are detectable on this date since most of the active chlorine has already recovered to its main reservoir species ClONO2. The observed values of ClOx and ClONO2 are in line with the established polar chlorine chemistry. The thermal equilibrium constants between the dimer formation and its dissociation, as derived from the balloon measurements, are on the lower side of reported data and in good agreement with values recommended by von Hobe et al. (2007). Calculations with the ECHAM/MESSy Atmospheric Chemistry model (EMAC) using established kinetics show similar chlorine activation and deactivation, compared to the measurements in January 2001 and March 2003, respectively.
Emissions of sulphur hexafluoride (SF6), one of the strongest greenhouse gases on a per molecule basis, are targeted to be collectively reduced under the Kyoto Protocol. Because of its long atmospheric lifetime (estimated as 800 to 3200 years), the accumulation of SF6 in the atmosphere is a direct measure of its global emissions. Examination of our extended data set of globally distributed high-precision SF6 observations shows an increase in SF6 abundance from near zero in the 1970s to a global mean of 6.7 ppt by the end of 2008. In-depth evaluation of our long-term data records shows that the global source of SF6 decreased after 1995, most likely due to SF6 emission reductions in industrialised countries, but increased again after 1998. By subtracting those emissions reported by Annex I countries to the United Nations Framework Convention of Climatic Change (UNFCCC) from our observation-inferred SF6 source leaves a surprisingly large gap of more than 70–80% of non-reported SF6 emissions in the last decade. This suggests a strong under-estimation of emissions in Annex I countries and underlines the urgent need for independent atmospheric verification of greenhouse gases emissions accounting.
Epoxyeicotrienoic acids (EETs) are cytochrome P450-dependent anti-hypertensive and anti-inflammatory derivatives of arachidonic acid, which are highly abundant in the kidney and considered reno-protective. EETs are degraded by the enzyme soluble epoxide hydrolase (sEH) and sEH inhibitors are considered treatment for chronic renal failure (CRF). We determined whether sEH inhibition attenuates the progression of CRF in the 5/6-nephrectomy model (5/6-Nx) in mice. 5/6-Nx mice were treated with a placebo, an ACE-inhibitor (Ramipril, 40 mg/kg), the sEH-inhibitor cAUCB or the CYP-inhibitor fenbendazole for 8 weeks. 5/6-Nx induced hypertension, albuminuria, glomerulosclerosis and tubulo-interstitial damage and these effects were attenuated by Ramipril. In contrast, cAUCB failed to lower the blood pressure and albuminuria was more severe as compared to placebo. Plasma EET-levels were doubled in 5/6 Nx-mice as compared to sham mice receiving placebo. Renal sEH expression was attenuated in 5/6-Nx mice but cAUCB in these animals still further increased the EET-level. cAUCB also increased 5-HETE and 15-HETE, which derive from peroxidation or lipoxygenases. Similar to cAUCB, CYP450 inhibition increased HETEs and promoted albuminuria. Thus, sEH-inhibition failed to elicit protective effects in the 5/6-Nx model and showed a tendency to aggravate the disease. These effects might be consequence of a shift of arachidonic acid metabolism into the lipoxygenase pathway.
Sacoglossan sea slugs are unique in the animal kingdom in that they sequester and maintain active plastids that they acquire from the siphonaceous algae upon which they feed, making the animals photosynthetic. While most sacoglossan species digest their freshly ingested plastids within hours, four species from the family Plakobranchidae retain their stolen plastids (kleptoplasts) in a photosynthetically active state on time scales of weeks to months. The molecular basis of plastid maintenance within the cytosol of digestive gland cells in these photosynthetic metazoans is yet unknown, but is widely thought to involve gene transfer from the algal food source to the slugs based upon previous investigations of single genes. Indeed, normal plastid development requires hundreds of nuclear-encoded proteins, with protein turnover in photosystem II in particular known to be rapid under various conditions. Moreover, only algal plastids, not the algal nuclei, are sequestered by the animals during feeding. If algal nuclear genes are transferred to the animal either during feeding or in the germ line, and if they are expressed, then they should be readily detectable with deep-sequencing methods. We have sequenced expressed mRNAs from actively photosynthesizing, starved individuals of two photosynthetic sea slug species, Plakobranchus ocellatus Van Hasselt, 1824 and Elysia timida Risso, 1818. We find that nuclear-encoded, algal-derived genes specific to photosynthetic function are expressed neither in P. ocellatus nor in E. timida. Despite their dramatic plastid longevity, these photosynthetic sacoglossan slugs do not express genes acquired from algal nuclei in order to maintain plastid function.
Methanogenic archaea are a group of strictly anaerobic microorganisms characterized by their strict dependence on the process of methanogenesis for energy conservation. Among the archaea, they are also the only known group synthesizing proteins containing selenocysteine or pyrrolysine. All but one of the known archaeal pyrrolysine-containing and all but two of the confirmed archaeal selenocysteine-containing protein are involved in methanogenesis. Synthesis of these proteins proceeds through suppression of translational stop codons but otherwise the two systems are fundamentally different. This paper highlights these differences and summarizes the recent developments in selenocysteine- and pyrrolysine-related research on archaea and aims to put this knowledge into the context of their unique energy metabolism.
The magnetic field sensors enabling birds to extract orientational information from the Earth’s magnetic field have remained enigmatic. Our previously published results from homing pigeons have made us suggest that the iron containing sensory dendrites in the inner dermal lining of the upper beak are a candidate structure for such an avian magnetometer system. Here we show that similar structures occur in two species of migratory birds (garden warbler, Sylvia borin and European robin, Erithacus rubecula) and a non-migratory bird, the domestic chicken (Gallus gallus). In all these bird species, histological data have revealed dendrites of similar shape and size, all containing iron minerals within distinct subcellular compartments of nervous terminals of the median branch of the Nervus ophthalmicus. We also used microscopic X-ray absorption spectroscopy analyses to identify the involved iron minerals to be almost completely Fe III-oxides. Magnetite (Fe II/III) may also occur in these structures, but not as a major Fe constituent. Our data suggest that this complex dendritic system in the beak is a common feature of birds, and that it may form an essential sensory basis for the evolution of at least certain types of magnetic field guided behavior.
Experimental results are presented for 180 in silico designed octapeptide sequences and their stabilizing effects on the major histocompatibility class I molecule H-2Kb. Peptide sequence design was accomplished by a combination of an ant colony optimization algorithm with artificial neural network classifiers. Experimental tests yielded nine H-2Kb stabilizing and 171 nonstabilizing peptides. 28 among the nonstabilizing octapeptides contain canonical motif residues known to be favorable for MHC I stabilization. For characterization of the area covered by stabilizing and non-stabilizing octapeptides in sequence space, we visualized the distribution of 100,603 octapeptides using a self-organizing map. The experimental results present evidence that the canonical sequence motives of the SYFPEITHI database on their own are insufficient for predicting MHC I protein stabilization.
Introduction: Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels. Methods: In Germany, patients receiving protein C concentrate (Ceprotin(R), Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this National, retrospective, multi-centered study. Results: Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03). Conclusions: This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.
Nep1 (Emg1) is a highly conserved nucleolar protein with an essential function in ribosome biogenesis. A mutation in the human Nep1 homolog causes Bowen–Conradi syndrome—a severe developmental disorder. Structures of Nep1 revealed a dimer with a fold similar to the SPOUT-class of RNA-methyltransferases suggesting that Nep1 acts as a methyltransferase in ribosome biogenesis. The target for this putative methyltransferase activity has not been identified yet. We characterized the RNA-binding specificity of Methanocaldococcus jannaschii Nep1 by fluorescence- and NMR-spectroscopy as well as by yeast three-hybrid screening. Nep1 binds with high affinity to short RNA oligonucleotides corresponding to nt 910–921 of M. jannaschii 16S rRNA through a highly conserved basic surface cleft along the dimer interface. Nep1 only methylates RNAs containing a pseudouridine at a position corresponding to a previously identified hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) in eukaryotic 18S rRNAs. Analysis of the methylated nucleoside by MALDI-mass spectrometry, HPLC and NMR shows that the methyl group is transferred to the N1 of the pseudouridine. Thus, Nep1 is the first identified example of an N1-specific pseudouridine methyltransferase. This enzymatic activity is also conserved in human Nep1 suggesting that Nep1 is the methyltransferase in the biosynthesis of m1acp3-Psi in eukaryotic 18S rRNAs.
Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5'-end) and complementary sequences in the 3'UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low.
The thermodynamics of base pairing is of fundamental importance. Fluorinated base analogs are valuable tools for investigating pairing interactions. To understand the influence of direct base–base interactions in relation to the role of water, pairing free energies between natural nucleobases and fluorinated analogs are estimated by potential of mean force calculations. Compared to pairing of AU and GC, pairing involving fluorinated analogs is unfavorable by 0.5–1.0 kcal mol -1. Decomposing the pairing free energies into enthalpic and entropic contributions reveals fundamental differences for Watson–Crick pairs compared to pairs involving fluorinated analogs. These differences originate from direct base–base interactions and contributions of water. Pairing free energies of fluorinated base analogs with natural bases are less unfavorable by 0.5–1.0 kcal mol -1 compared to non-fluorinated analogs. This is attributed to stabilizing C–F…H–N dipolar interactions and stronger N…H–C hydrogen bonds, demonstrating direct and indirect influences of fluorine. 7-methyl-7H-purine and its 9-deaza analog (Z) have been suggested as members of a new class of non-fluorinated base analogs. Z is found to be the least destabilizing universal base in the context of RNA known to date. This is the first experimental evidence for nitrogen-containing heterocylces as bioisosteres of aromatic rings bearing fluorine atoms.
Within the present study the occurrence and fate of the organophosphorus flame retardants and plasticizers tris(2-chloroethyl) phosphate (TCEP), tris(2-chloro-1-methylethyl) phosphate (TCPP), tris(1,3-dichloro-2-propyl) phosphate (TDCP), tris(2-butoxyethyl) phosphate (TBEP), tri-iso-butyl phosphate (TiBP), and tri-n-butyl phosphate (TnBP) in precipitation, lake water, surface runoff and groundwater from urban and remote areas in Germany was investigated between June 2007 and October 2009. 255 samples of precipitation, 210 samples of lentic surface water and 72 samples of groundwater were analyzed for the six organophosphates (OPs) by solid phase extraction followed by gas chromatography-mass spectrometry. The research focused on aspects concerning (1) the atmospheric washout of OPs by precipitation, (2) the temporal variation of OP concentrations in precipitation and in lentic surface waters as well as (3) the pollution of groundwater by OPs. The results of the study emphasize the importance of precipitation as an all-season entry-pathway for OPs in the aquatic environment, particularly in densely populated urban environments with high traffic volume and abundant usage of flame-protected products. No seasonal trends were observed for all analytes in precipitation at the urban sampling site. TCPP dominated in all precipitation and storm water holding tank (SWHT) water samples with maximum levels exceeding 1 µg/L. An accumulation of OPs deposited in SWHTs was observed with concentrations often exceeding those observed in wet precipitation. Median concentrations of TCPP (880 ng/L), TDCP (13 ng/L), and TBEP (77 ng/L) at the urban SWHT were more than twice as high as those measured at the urban precipitation sampling site (403 ng/L, 5 ng/L, 21 ng/L) located close to the SWHT. OP levels in more remote lakes were often below or close to the limits of quantitation (LOQ). Nevertheless, TCPP was the substance with the highest median concentration in rural volcanic lakes (7–18 ng/L) indicating an atmospheric transport of the compound. At urban lakes the median OP concentrations were in the range of 23–61 ng/L (TCEP), 85–126 ng/L (TCPP), <LOQ–53 ng/L (TBEP), 8–10 ng/L (TiBP), and 17–32 ng/L (TnBP). In laboratory experiments, TBEP, TiBP, and TnBP were photochemically degraded in spiked lake water samples upon exposure to sunlight. In the SWHT a seasonal trend with decreasing concentrations in summer/autumn was evident for TiBP and TnBP but not for the chlorinated OPs. The decreasing concentrations can be explained by in-lake photodegradation. Results have also shown that the occurrence of OPs in groundwater is depending on the anthropogenic impact during groundwater recharge/natural replenishment. Infiltration of precipitation was found to be no important entry-pathway for OPs into aquifers at rural sites. Highest OP concentrations (>0.1 µg/L) were determined in groundwater polluted by percolating leachate from contaminated sites or groundwater recharged via bank filtration of OP-loaded recipients. Concentrations of TCEP, TCPP, TiBP and TnBP in groundwater decreased rapidly (89–97%) during bank filtration with increasing distance from the recipient due to adsorption processes and/or biotransformation. Although TCEP and TCPP are stable within the aquifer, they are not suitable as conservative organic tracers in groundwater.
We presented a proof for the classical stable limit laws under use of contraction method in combination with the Zolotarev metric. Furthermore, a stable limit law was proved for scaled sums of growing into sequences. This limit law was alternatively formulated for sequences of random variables defined by a simple degenerate recursion.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Background: Local adaptation to divergent environmental conditions can promote population genetic differentiation even in the absence of geographic barriers and hence, lead to speciation. Perturbations by catastrophic events, however, can distort such parapatric ecological speciation processes. Here, we asked whether an exceptionally strong flood led to homogenization of gene pools among locally adapted populations of the Atlantic molly (Poecilia mexicana, Poeciliidae) in the Cueva del Azufre system in southern Mexico, where two strong environmental selection factors (darkness within caves and/or presence of toxic H2S in sulfidic springs) drive the diversification of P. mexicana. Nine nuclear microsatellites as well as heritable female life history traits (both as a proxy for quantitative genetics and for trait divergence) were used as markers to compare genetic differentiation, genetic diversity, and especially population mixing (immigration and emigration) before and after the flood. Results: Habitat type (i.e., non-sulfidic surface, sulfidic surface, or sulfidic cave), but not geographic distance was the major predictor of genetic differentiation. Before and after the flood, each habitat type harbored a genetically distinct population. Only a weak signal of individual dislocation among ecologically divergent habitat types was uncovered (with the exception of slightly increased dislocation from the Cueva del Azufre into the sulfidic creek, El Azufre). By contrast, several lines of evidence are indicative of increased flood-induced dislocation within the same habitat type, e.g., between different cave chambers of the Cueva del Azufre. Conclusions: The virtual absence of individual dislocation among ecologically different habitat types indicates strong natural selection against migrants. Thus, our current study exemplifies that ecological speciation in this and other systems, in which extreme environmental factors drive speciation, may be little affected by temporary perturbations, as adaptations to physico-chemical stressors may directly affect the survival probability in divergent habitat types.
Background: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky [greater than or equal to]60% / Child-Pugh [less than or equal to]12) were randomised to receive thymostimulin 75 mg s.c. 5x/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. Current Controlled Trials ISRCTN64487365. Results: Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p=0.87, HR=1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p=0.60, HR=1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions: In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. trial registration: Current Controlled Trials ISRCTN64487365
Background: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced during hemorrhagic shock and resuscitation (H/R), which may contribute to multiple organ failure. The AIM of this study was to test the hypothesis that green tea (Camellia sinenesis) extract containing 85% polyphenols decreases injury after H/R in rats by scavenging ROS and RNS. Method: S: Female Sprague Dawley rats were given 100 mg polyphenol extract/kg body weight or vehicle 2 h prior to hemorrhagic shock. H/R was induced by two protocols: 1) withdrawal of blood to a mean arterial pressure of 40 mm Hg followed by further withdrawals to decrease blood pressure progressively to 28 mm Hg over 1 h (severe), and 2) withdrawal of blood to a sustained hypotension of 40 mm Hg for 1 h (moderate). Rats were then resuscitated over 1 h with 60% of the shed blood volume plus twice the shed blood volume of lactated Ringer's solution. Serum samples were collected at 10 min and 2 h after resuscitation. At 2 or 18 h, livers were harvested for cytokine and 3-nitrotyrosine quantification, immunohistochemical detection of 4-hydroxynonenol (4-HNE) and inducible nitric oxide synthase (iNOS) protein expression. Results: After severe H/R, 18-h survival increased from 20% after vehicle to 70% after polyphenols (p<0.05). After moderate H/R, survival was greater (80%) and not different between vehicle and polyphenols. In moderate H/R, serum alanine aminotransferase (ALT) increased at 10 min and 2 h postresuscitation to 345 and 545 IU/L, respectively. Polyphenol treatment blunted this increase to 153 and 252 IU/L at 10 min and 2 h (p<0.01). Polyphenols also blunted increases in liver homogenates of TNFalpha (7.0 pg/mg with vehicle vs. 4.9 pg/mg with polyphenols, p<0.05), IL-1beta (0.80 vs. 0.37 pg/mg, p<0.05), IL-6 (6.9 vs. 5.1 pg/mg, p<0.05) and nitrotyrosine (1.9 pg/mg vs. 0.6 pg/mg, p<0.05) measured 18 h after H/R. Hepatic 4-HNE immunostaining indicative of lipid peroxidation also decreased from 4.8% after vehicle to 1.5% after polyphenols (p<0.05). By contrast, polyphenols did not block increased iNOS expression at 2 h after H/R. CONCLUSION: Polyphenols decrease ROS/RNS formation and are beneficial after hemorrhagic shock and resuscitation.
Background: Because Endomyocardial Biopsy has low sensitivity of about 20%, it can be performed near to myocardium that presented as Late Gadolinium Enhancement (LGE) in cardiovascular magnetic resonance (CMR). However the important issue of comparing topography of CMR and histological findings has not yet been investigated. Thus the current study was performed using an animal model of myocarditis. Results: In 10 male Lewis rats Experimental Autoimmune myocarditis was induced, 10 rats served as control. On day 21 animals were examined by CMR to compare topographic distribution of LGE to histological inflammation. Sensitivity, specificity, positive and negative predictive values for LGE in diagnosing myocarditis were determined for each segment of myocardium. Latter diagnostic values varied widely depending on topographic distribution of LGE and inflammation as well as on the used CMR sequence. Sensitivity of LGE was up to 76% (left lateral myocardium) and positive predictive values were up to 85% (left lateral myocardium), whereas sensitivity and positive predictive value dropped to 0 - 33% (left inferior myocardium). Conclusions: Topographic distribution of LGE and histological inflammation seem to influence sensitivity, specifity, positive and negative predictive values. Nevertheless, positive predictive value for LGE of up to 85% indicates that Endomyocardial Biopsy should be performed "MR-guided". LGE seems to have greater sensitivity than Endomyocardial Biopsy for the diagnosis of myocarditis.
Clathrates are candidate materials for thermoelectric applications because of a number of unique properties. The clathrate I phases in the Ba-Ni-Ge ternary system allow controlled variation of the charge carrier concentration by adjusting the Ni content. Depending on the Ni content, the physical properties vary from metal-like to insulator-like and show a transition from p-type to n-type conduction. Here we present first results on the characterization of millimeter-sized single crystals grown by the Bridgman technique. Single crystals with a composition of Ba8Ni3.5Ge42.1h0.4 show metallic behavior (dp/dT > 0) albeit with high resistivity at room temperature [p (300 K) = 1 mOhm cm]. The charge carrier concentration at 300 K, as determined from Hall-effect measurements, is 2.3 e-/unit cell. The dimensionless thermoelectric figure of merit estimated at 680 K is ZT ~ 0.2. Keywords Clathrates - thermoelectric material - intermetallic compound - nickel