Recovery index, attentiveness and state of memory after xenon or isoflurane anaesthesia: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Performance of patients immediately after anaesthesia is an area of special interest and so a clinical trial was conducted to compare Xenon with Isoflurane anaesthesia. In order to assess the early cognitive recovery the syndrome short test (SST) according to Erzigkeit (Geromed GmbH) was applied.</p> <p>Methods</p> <p>ASA I and II patients undergoing long and short surgical interventions were randomised to receive either general anaesthesia with Xenon or Isoflurane. The primary endpoint was the validated SST which covering memory disturbances and attentiveness. The test was used on the day prior to intervention, one and three hours post extubation. The secondary endpoint was the recovery index (RI) measured after the end of the inhalation of Xenon or Isoflurane. In addition the Aldrete score was evaluated up to 180 min. On the first post-operative day the patients rated the quality of the anaesthetic using a scoring system from 1-6.</p> <p>Results</p> <p>The demographics of the groups were similar. The sum score of the SST delivered a clear trend one hour post extubation and a statistically significant superiority for Xenon three hours post extubation (p < 0.01). The RI likewise revealed a statistically significant superiority of Xenon 5 minutes post extubation (p < 0.01). The Aldrete score was significantly higher for 45 min. The scoring system results were also better after Xenon anaesthesia (p < 0.001).</p> <p>Conclusions</p> <p>The results show that recovery from anaesthesia and the early return of post-operative cognitive functions are significantly better after Xenon anaesthesia compared to Isoflurane. The results of the RI for Xenon are similar with the previously published results.</p> <p>Trial Registration</p> <p>The trial was registered with the number ISRCTN01110844 <url>http://www.controlled-trials.com/isrctn/pf/01110844</url>.</p

Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

Prostate-specific antigen testing in Tyrol, Austria: prostate cancer mortality reduction was supported by an update with mortality data up to 2008

Objectives: The objective of this study was to update an in-depth analysis of the time trend for prostate cancer (PCA) mortality in the population of Tyrol by 5 years, namely to 2008. In Tyrol, prostate-specific antigen (PSA) tests were introduced in 1988/89; more than three-quarters of all men in the age group 45–74 had at least one PSA test in the past decade. Methods: We applied the same model as in a previous publication, i.e., an age-period-cohort model using Poisson regression, to the mortality data covering more than three decades from 1970 to 2008. Results: For Tyrol from 2004 to 2008 in the age group 60+ period terms show a significant reduction in prostate cancer mortality with a risk ratio of 0.70 (95% confidence interval 0.57, 0.87) for Tyrol, and for Austria excluding Tyrol a moderate reduction with a risk ratio of 0.92 (95% confidence interval 0.87, 0.97), each compared to the mortality rate in the period 1989–1993. Conclusions: This update strengthens our previously published results, namely that PSA testing offered to a population at no charge can reduce prostate cancer mortality. The extent of mortality reduction is in line with that reported in the other recent publications. However, our data do not permit us to fully assess the harms associated with PCA screening, and no recommendation for PSA screening can be made without a careful evaluation of overdiagnosis and overtreatment

Articular cartilage mineralization in osteoarthritis of the hip

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the frequency of articular cartilage calcification in patients with end-stage hip OA. Further, its impact on the clinical situation and the OA severity are analyzed.</p> <p>Methods</p> <p>Eighty patients with OA of the hip who consecutively underwent total hip replacement were prospectively evaluated, and 10 controls were included. The patients' X-rays were analyzed for the presence of articular cartilage mineralization. A Harris Hip Score (HHS) was preoperatively calculated for every patient.</p> <p>Slab specimens from the femoral head of bone and cartilage and an additional square centimeter of articular cartilage from the main chondral defect were obtained from each patient for analysis of mineralization by digital contact radiography (DCR). Histological grading was also performed. In a subset of 20 patients, minerals were characterized with an electron microscope (FE-SEM).</p> <p>Results</p> <p>Calcifications were seen in all OA cartilage and slab specimens using DCR, while preoperative X-rays revealed calcification in only 17.5%. None of the control cartilage specimens showed mineralization. There was a highly significant inverse correlation between articular cartilage calcification and preoperative HHS. Histological OA grade correlated positively with the amount of matrix calcification. FE-SEM analysis revealed basic calcium phosphate (BCP) as the predominant mineral; CPPD crystals were found in only two patients.</p> <p>Conclusions</p> <p>Articular cartilage calcification is a common event in osteoarthritis of the hip. The amount of calcification correlates with clinical symptoms and histological OA grade.</p

Single Mode Lasing from Hybrid Hemispherical Microresonators

Enormous attention has been paid to optical microresonators which hold a great promise for microlasers as well as fundamental studies in cavity quantum electrodynamics. Here we demonstrate a three-dimensional (3D) hybrid microresonator combining self-assembled hemispherical structure with a planar reflector. By incorporating dye molecules into the hemisphere, optically pumped lasing phenomenon is observed at room temperature. We have studied the lasing behaviors with different cavity sizes, and particularly single longitudinal mode lasing from hemispheres with diameter ∼15 μm is achieved. Detailed characterizations indicate that the lasing modes shift under varying pump densities, which can be well-explained by frequency shift and mode hopping. This work provides a versatile approach for 3D confined microresonators and opens an opportunity to realize tunable single mode microlasers

Cytotoxic activity of proteins isolated from extracts of Corydalis cava tubers in human cervical carcinoma HeLa cells

<p>Abstract</p> <p>Background</p> <p><it>Corydalis cava </it>Schweigg. & Koerte, the plant of numerous pharmacological activities, together with the studied earlier by our group <it>Chelidonium majus </it>L. (Greater Celandine), belong to the family <it>Papaveraceae</it>. The plant grows in Central and South Europe and produces the sizeable subterraneous tubers, empty inside, which are extremely resistant to various pathogen attacks. The <it>Corydalis sp. </it>tubers are a rich source of many biologically active substances, with the extensive use in European and Asian folk medicine. They have analgetic, sedating, narcotic, anti-inflammatory, anti-allergic and anti-tumour activities. On the other hand, there is no information about possible biological activities of proteins contained in <it>Corydalis cava </it>tubers.</p> <p>Methods</p> <p>Nucleolytic proteins were isolated from the tubers of <it>C. cava </it>by separation on a heparin column and tested for DNase activity. Protein fractions showing nucleolytic activity were tested for cytotoxic activity in human cervical carcinoma HeLa cells. Cultures of HeLa cells were conducted in the presence of three protein concentrations: 42, 83 and 167 ng/ml during 48 h. Viability of cell cultures was appraised using XTT colorimetric test. Protein fractions were separated and protein bands were excised and sent for identification by mass spectrometry (LC-ESI-MS/MS).</p> <p>Results</p> <p>The studied protein fractions showed an inhibiting effect on mitochondrial activity of HeLa cells, depending on the administered dose of proteins. The most pronounced effect was obtained with the highest concentration of the protein (167 ng/ml) - 43.45 ± 3% mitochondrial activity of HeLa cells were inhibited. Mass spectrometry results for the proteins of applied fractions showed that they contained plant defense- and pathogenesis-related (PR) proteins.</p> <p>Conclusions</p> <p>The cytotoxic effect of studied proteins toward HeLa cell line cells has been evident and dependent on increasing dose of the protein. The present study, most probably, represents the first investigations on the effect of purified PR proteins from tuber extracts of a pharmacologically active plant on cell lines.</p

When does the co-evolution of technology and science overturn into technoscience?

In this paper, the relations between science and technology, intervention and representation, the natural and the artificial are analysed on the background of the formation of modern science in the sixteenth century. Due to the fact that technique has been essential for modern science from its early beginning, modern science is characterised by a hybridisation of knowledge and intervention. The manipulation of nature in order to measure its properties has steadily increased until artificial things have been produced, such as laser beams, chemical compounds, elementary particles. Furthermore, the structural bracing of natural science, technological development, and industrial exploitation of nature go also back to the foundation of modern science. In order to strengthen the debate on technoscience against this background, the specific characteristics of technoscientific objects have to be clarified as have the specific characteristics of the social organisation of technoscience and its performance

Molecular Determinants of S100B Oligomer Formation

Background: S100B is a dimeric protein that can form tetramers, hexamers and higher order oligomers. These forms have been suggested to play a role in RAGE activation. Methodology/Principal Findings: Oligomerization was found to require a low molecular weight trigger/cofactor and could not be detected for highly pure dimer, irrespective of handling. Imidazol was identified as a substance that can serve this role. Oligomerization is dependent on both the imidazol concentration and pH, with optima around 90 mM imidazol and pH 7, respectively. No oligomerization was observed above pH 8, thus the protonated form of imidazol is the active species in promoting assembly of dimers to higher species. However, disulfide bonds are not involved and the process is independent of redox potential. The process was also found to be independent of whether Ca 2+ is bound to the protein or not. Tetramers that are purified from dimers and imidazol by gel filtration are kinetically stable, but dissociate into dimers upon heating. Dimers do not revert to tetramer and higher oligomer unless imidazol is again added. Both tetramers and hexamers bind the target peptide from p53 with retained stoichiometry of one peptide per S100B monomer, and with high affinity (lgK = 7.360.2 and 7.260.2, respectively in 10 mM BisTris, 5 mM CaCl 2, pH 7.0), which is less than one order of magnitude reduced compared to dimer under the same buffer conditions. Conclusion/Significance: S100B oligomerization requires protonated imidazol as a trigger/cofactor. Oligomers ar