Novel α-glycosyl compounds from glycosylation of rubusoside.

In this work we investigated mixtures from α-glycosylation of rubusoside with cyclodextrin glycosyltransferases. In addition to the previously known α-1,4 glycosylated derivatives, nine new compounds with rare α-1,3-glycosidic bonds were identified based on nuclear magnetic resonance spectroscopy and mass spectrometric analysis. Furthermore, sensory properties of monoglycosylated rubusoside derivatives were investigated and compared to previously described monoglycosylated compounds. Additionally, digestion with α-amylase from human saliva was investigated for different glycosylated rubusoside derivatives.

[Precancerous and early stage cancer of the bile duct system]. / Präkanzerosen und Frühkarzinome des Gallengangsystems.

Early stage cancer of the bile duct system is still difficult to diagnose. In cases of suspect lesions a stepwise diagnostic procedure consisting of computed tomography (CT), magnetic resonance imaging (MRI) with MR cholangiography (MRC) and possibly endoscopic retrograde cholangiopancreatography (ERCP) with brush cytology should immediately be carried out. If there is a sufficient suspicion for premalignancy or early stage cancer the indications for surgical intervention should clearly be defined. Only resection can lead to a decrease in the recurrence rate and a better long-term outcome. If the patient is in a functionally nonresectable condition the possibility of liver transplantation should be considered.

Mouse white adipose tissue-derived mesenchymal stem cells gain pericentral and periportal hepatocyte features after differentiation in vitro, which are preserved in vivo after hepatic transplantation.

AIM: Mesenchymal stem cells may differentiate into hepatocyte-like cells in vitro and in vivo. Therefore, they are considered a novel cell resource for the treatment of various liver diseases. Here, the aim was to demonstrate that mesenchymal stem cells may adopt both perivenous and periportal hepatocyte-specific functions in vitro and in vivo. METHODS: Adipose tissue-derived mesenchymal stem cells were isolated from immunodeficient C57BL/6 (B6.129S6-Rag2(tm1Fwa) Prf1(tm1Clrk) ) mice and differentiated into the hepatocytic phenotype by applying a simple protocol. Their physiological and metabolic functions were analysed in vitro and after hepatic transplantation in vivo. RESULTS: Mesenchymal stem cells changed their morphology from a fibroblastoid into shapes of osteocytes, chondrocytes, adipocytes and hepatocytes. Typical for mesenchymal stem cells, hematopoietic marker genes were not expressed. CD90, which is not expressed on mature hepatocytes, decreased significantly after hepatocytic differentiation. Markers indicative for liver development like hepatic nuclear factor 4 alpha, or for perivenous hepatocyte specification like cytochrome P450 subtype 3a11, and CD26 were significantly elevated. Periportal hepatocyte-specific markers like carbamoylphosphate synthetase 1, the entry enzyme of the urea cycle, were up-regulated. Consequently, cytochrome P450 enzyme activity and urea synthesis increased significantly to values comparable to cultured primary hepatocytes. Both perivenous and periportal qualities were preserved after hepatic transplantation and integration into the host parenchyma. CONCLUSIONS: Adult mesenchymal stem cells from adipose tissue differentiated into hepatocyte-like cells featuring both periportal and perivenous functions. Hence, they are promising candidates for the treatment of region-specific liver cell damage and may support organ regeneration in acute and chronic liver diseases.

Managing Spatial Selections With Contextual Snapshots.

Spatial selections are a ubiquitous concept in visualization. By localizing particular features, they can be analysed and compared in different views. However, the semantics of such selections often depend on specific parameter settings and it can be difficult to reconstruct them without additional information. In this paper, we present the concept of contextual snapshots as an effective means for managing spatial selections in visualized data. The selections are automatically associated with the context in which they have been created. Contextual snapshots can also be used as the basis for interactive integrated and linked views, which enable in-place investigation and comparison of multiple visual representations of data. Our approach is implemented as a flexible toolkit with well-defined interfaces for integration into existing systems. We demonstrate the power and generality of our techniques by applying them to several distinct scenarios such as the visualization of simulation data, the analysis of historical documents and the display of anatomical data.

Isolation and hepatocyte differentiation of mesenchymal stem cells from porcine bone marrow--"surgical waste" as a novel MSC source.

Mesenchymal stem cells (MSC) isolated from bone marrow and differentiated into hepatocyte-like cells have increasingly gained attention for clinical cell therapy of liver diseases because of their high regenerative capacity. They are available from bone marrow aspirates of the os coxae after puncture of the crista iliaca or from bone marrow "surgical waste" gained from amputations or knee and hip operations. Thus, the aim of the study was to demonstrate whether these pBM-MSC (porcine bone marrow-derived mesenchymal stem cells) displayed mesenchymal features and hepatocyte differentiation potential. MSC were isolated either from crista iliaca punctures or after sampling and collagenase digestion of bone marrow from the os femoris. Mesenchymal features were assessed by flow cytometry for specific surface antigens and their ability to differentiate into at least 3 lineages. Functional properties, such as urea or glycogen synthesis and cytochrome P450 activity, as well as the cell morphology were examined during hepatocyte differentiation. pBM-MSC from both sources lacked the hematopoietic markers CD14 and CD45 but expressed the typical mesenchymal markers CD44, CD29, CD90, and CD105. Both cell types could differentiate into adipocyte, osteocyte, and hepatocyte lineages. After hepatocyte differentiation, CD105 expression decreased significantly and cells changed morphology from fibroblastoid into polygonal, displaying significantly increased glycogen storage, urea synthesis, and cytochrome activity. pBM-MSC from various sources were identical in respect to their mesenchymal features and their hepatocyte differentiation potential. Hence, long bones might be a particularly useful resource to isolate bone marrow mesenchymal stem cells for transplantation.

Comparing the after-effects of continuous theta burst stimulation and conventional 1 Hz rTMS on semantic processing.

Our aim was to evaluate continuous theta burst stimulation (cTBS) as a tool to induce temporary impairment (virtual lesion) in semantic processing. Four groups with 20 subjects each were stimulated. In the three experimental groups the stimulation site was the left superior temporal cortex. Stimulation was either 1Hz repetitive transcranial magnetic stimulation (rTMS) at 100% resting motor threshold (RMT) or cTBS, with intensities of 80% or 90% active motor threshold (AMT). The TMS-control group was stimulated at the right medial prefrontal cortex with 1 Hz rTMS. After stimulation subjects accomplished a lexical decision task with a duration of about 20 min. In an additional fifth group the lexical decision task was performed without TMS. Reaction times were not influenced by cTBS applied with 80% AMT, but prolonged for about 80 ms with 90% AMT compared to the no stimulation condition. An increase of 140 ms was found after 1 Hz rTMS. The effect lasted for the whole task, but declined from the first to the second half of the experiment. The direct comparison of cTBS and 1 Hz rTMS suggests that both stimulation patterns can induce virtual lesions in the left superior temporal cortex and impair semantic processing. We suppose that cTBS could replace 1 Hz rTMS in this field since the application is faster and it is more comfortable to the subjects.

Nanofiber Fabry-Perot microresonator for nonlinear optics and cavity quantum electrodynamics.

We experimentally realize a Fabry-Perot-type optical microresonator near the cesium D2 line wavelength based on a tapered optical fiber, equipped with two fiber Bragg gratings that enclose a subwavelength diameter waist. Owing to the very low taper losses, the finesse of the resonator reaches F=86 while the on-resonance transmission is T=11%. The characteristics of our resonator fulfill the requirements of nonlinear optics and cavity quantum electrodynamics in the strong coupling regime. These characteristics, combined with the demonstrated ease of use and advantageous mode geometry, open a realm of applications.

Generation of flattop pump pulses for OPCPA by coherent pulse stacking with fiber Bragg gratings.

We present a simple and robust pulse shaping device based on coherent pulse stacking. The device is embedded in a polarisation maintaining step index fiber. An input pulse is sent through a fiber optical circulator. Up to four pulse replicas are reflected by fiber Bragg gratings and interfere at the output. Temperature control allows tuning of the relative pulse phases of the sub-pulses. Additionally fine tuning of the sub-pulse amplitudes is demonstrated. We experimentally generated 235 ps and 416 ps long flattop pulses with rising and falling edges shorter than 100 ps. In contrast to other pulse shaping techniques the presented setup is robust, alignment free, provides excellent beam quality and is also suitable for pulse durations up to several nanoseconds.

Fast firing of tiles containing paper mill sludge, glass cullet and clay.

The paper describes results obtained in the development of a previous research. We study here, in fast firing, the sintering behaviour and measure some properties of tiles containing a mixture of 60 wt% of paper mill sludge and 40 wt% of glass cullet. The behaviour of this material is compared to those displayed by materials obtained by the same mixture added with 10, 20 and 30 wt% of a natural red clay. In parallel, the same properties are measured also on a reference blend, which is presently used to produce commercial tiles. We show that powders containing 60 wt% of paper sludge and 40 wt% of glass cullet to which 30 wt% of clay is added give rise to materials that display a stable sintering process and have good hardness and strength and therefore could be used for the industrial production of tiles.

Less favorable clinical outcome after diagnostic and interventional double balloon enteroscopy in patients with suspected small-bowel bleeding?

BACKGROUND AND STUDY AIMS: Double balloon enteroscopy (DBE) is a new endoscopic technique that allows diagnosis and therapeutic interventions of small-bowel lesions. One of the main indications for DBE is suspected small-bowel bleeding (SSBB). Data about clinical outcome after DBE are limited. The aim of the present study was to prospectively assess the short-term clinical outcome of this procedure. PATIENTS AND METHODS: Of all consecutive patients undergoing DBE for various indications, follow-up results in patients with SSBB were analyzed. Standardized questionnaires were used, including assessment of gastrointestinal symptoms, especially signs of gastrointestinal bleeding, blood transfusions, demand for re-intervention, and hospitalization. RESULTS: Of a total of 180 DBEs performed in 124 patients during a 2-year period, SSBB was the indication in 84 patients (M/F = 46/38; mean age 63 years) who underwent a total of 111 DBEs. Of these patients 52 could be followed (mean follow-up 2 months, range 1-5 months). In this subgroup, positive findings were obtained in 30 (mostly angiodysplasia), with therapeutic interventions being performed in 18 of these patients. At follow-up, the rate of re-bleeding in patients who had undergone interventions (20%) was similar to that in patients who had not (18%). CONCLUSION: In this pilot study, DBE did not seem to have a major effect on re-bleeding. Better patient selection or modification of therapeutic regimens appears to be necessary to better utilize DBE in SSBB.

Production and characterization of sintered ceramics from paper mill sludge and glass cullet.

Three different types of paper mill sludge were first incinerated and then attrition milled separately or mixed with glass cullet in varying proportions to obtain powders of different compositions. These powders were then dried, sieved, uniaxially pressed into samples and air sintered. Fired samples were characterized by density, water absorption, shrinkage on firing, strength, hardness and fracture toughness measurements; SEM and X-ray diffractions were also carried out to investigate microstructure and phase composition. Some sintered samples displayed fairly good physical and mechanical properties as a consequence of their low residual porosity and fine microstructure.

Development and evaluation of a video program for presentation prior to elective cardiac surgery.

BACKGROUND: : The objective of the present study was to develop and evaluate the effects of a preparatory videotape on endocrine stress responses of patients prior to cardiac surgery and to analyze patient acceptance of this video for preoperative preparation. METHODS: : 101 male patients prior to elective cardiac surgery were enrolled into the study. On the day before surgery, patients were assigned to one of the following groups: group 1 (n = 51) saw a video with realistic information about the upcoming perioperative procedure, and group 2 (n = 50) saw a video of the same length without surgery-related information. Venous blood was sampled before and 15 min after the video presentation. On the second postoperative day, patients filled in a questionnaire concerning their experiences of having preoperatively watched the video. RESULTS: : After viewing the video, blood levels of cortisol, adrenocorticotropic hormone (ACTH), beta-endorphin, prolactin, epinephrine and norepinephrine in patients of group 1 were not significantly different compared to values measured before the video presentation. In patients of group 2, blood levels of cortisol, ACTH, prolactin and norepinephrine were significantly lower after video presentation compared to values obtained before the video. Patients of group 1 (compared to group 2) were significantly more often of the opinion that the video had helped in the preparation for surgery, and that they would like to repeat this adjunct preoperative video preparation in another similar situation. CONCLUSION: : We conclude from our results that (i); cardiac surgical patients prefer preoperatively an adjunct surgery-related video preparation to a non-specific video presentation, and that (ii); preoperative preparation with realistic information about the upcoming medical procedure in patients undergoing cardiac surgery does not lead to an increase in endocrine stress hormone levels.

The fungal biocontrol agent Coniothyrium minitans: production by solid-state fermentation, application and marketing.

Biological control agents (BCAs) are potential alternatives for the chemical fungicides presently used in agriculture to fight plant diseases. Coniothyrium minitans is an example of a promising fungal BCA. It is a naturally occurring parasite of the fungus Sclerotinia sclerotiorum, a wide-spread pathogen which substantially reduces the yield of many crops. This review describes, exemplified by C. minitans, the studies that need to be carried out before a fungal BCA is successfully introduced into the market. The main aspects considered are the biology of C. minitans, the development of a product by mass production of spores using solid-state fermentation technology, its biocontrol activity and marketing of the final product.

JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in nerve growth factor-deprived sympathetic neurons.

The stress activated protein kinase pathway culminates in c-Jun phosphorylation mediated by the Jun Kinases (JNKs). The role of the JNK pathway in sympathetic neuronal death is unclear in that apoptosis is not inhibited by a dominant negative protein of one JNK kinase, SEK1, but is inhibited by CEP-1347, a compound known to inhibit this overall pathway but not JNKs per se. To evaluate directly the apoptotic role of the JNK isoform that is selectively expressed in neurons, JNK3, we isolated sympathetic neurons from JNK3-deficient mice and quantified nerve growth factor (NGF) deprivation-induced neuronal death, oxidative stress, c-Jun phosphorylation, and c-jun induction. Here, we report that oxidative stress in neurons from JNK3-deficient mice is normal after NGF deprivation. In contrast, NGF-deprivation-induced increases in the levels of phosphorylated c-Jun, c-jun, and apoptosis are each inhibited in JNK3-deficient mice. Overall, these results indicate that JNK3 plays a critical role in activation of c-Jun and apoptosis in a classic model of cell-autonomous programmed neuron death.

Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass.

Cardiac surgery with cardiopulmonary bypass (CPB) leads to a systemic inflammatory response with secretion of cytokines (e.g. IL-6, TNF-alpha, IL-1 beta and sIL-2R). The objective of the following study was to investigate in vitro and in vivo cytokine responses and white blood cell counts (WBC) of patients with high versus low cytokine secretion after a coronary artery bypass grafting (CABG) procedure. Twenty male patients undergoing elective CABG surgery with CPB under general anaesthesia were enrolled in the study. On the day of surgery (postoperatively), serum levels of TNF-alpha and IL-1 beta were significantly higher in patients of the high IL-6 level group compared to the respective values in the patient group with low IL-6 levels. The inter-individual differences in IL-6 release in patients undergoing CABG surgery with CPB were accompanied by differences in the release of other cytokines, such as TNF-alpha, IL-1 beta and sIL-2R. To understand whether genetic background plays a role in influencing cytokine plasma levels under surgical stress, we examined the distribution of polymorphic elements within the promoter regions of the TNF-alpha and IL-6 genes, and determined their genotype regarding the BAT2 gene and TNF-beta intron polymorphisms. Our preliminary data suggests that regulatory polymorphisms in or near the TNF locus, more precisely the allele set 140/150 of the BAT2 microsatellite marker combined with the G allele at -308 of the TNF-alpha gene, could be one of the genetic constructions providing for a less sensitive response to various stimuli. Our results suggest: (1) close relationships between cytokine release in the postoperative period, and (2) inter-individually varying patterns of cytokine release in patients undergoing CABG surgery with CPB.

Antiphospholipid antibodies in children without and in adults with and without thrombophilia.

Antiphospholipid antibodies (APAs) are considered risk factors in patients with thromboembolic diseases. Although the incidence of such acquired coagulation disturbances in adults are well described, only few data exist for children. Therefore, in a first step to collect new data we analyzed the presence of different APAs in 202 consecutive children and compared them with two groups of adults. The children screened for APA were exclusively those who did not have any thromboembolic complications or a tendency for thrombophilia due to other underlying diseases such as systemic lupus or malignancy in their past or present medical history. Consecutive blood samples were evaluated from routine laboratory specimens. The two groups of adults comprised 200 patients after deep vein thrombosis and 200 patients without thromboembolic events that served as controls. Four lupus anticoagulant (LA) screening tests were determined: the dilute Russell's viper venom test; a lupus anticoagulant-sensitive activated partial thromboplastin time reagent; a second lupus-sensitive activated partial thromboplastin time; and the Kaolin clotting time. Furthermore, three different antiphospholipid antibodies ELISA assays against cardiolipin (ACA), beta2-glycoprotein I, and phosphatidyl-serine, were determined. The children had a much higher prevalence for LA than did the adults. On the other hand, their values for ACA were significantly lower than in adults with a history of thromboembolism. Findings in children were similar to the normal adult group. This has to be taken into account when evaluating children with thromboembolic diseases.

Effect of GABA on the processing of interaural time differences in nucleus laminaris neurons in the chick.

Neurons in the avian nucleus laminaris (NL) are the first to receive binaural information and are presumed to play a role in encoding interaural time differences (ITD). NL not only receives excitatory projections from the ipsi- and contralateral nucleus magnocellularis, but also receives inhibitory (GABAergic) input. This study investigates how GABA (gamma-aminobutyric acid) influences ITD coding in NL. Intracellular responses of chick NL neurons were studied in a brain slice preparation. Both excitatory inputs to NL were electrically activated and the delay between trains of bilateral stimuli (simulated-interaural time difference [s-ITD]) was varied. The resulting s-ITD functions were recorded in the presence of 0-75 microM GABA. The discharge rate of NL neurons varied with s-ITD. Cells responded maximally using s-ITDs at which the peak of the ipsi- and contralateral excitatory postsynaptic potentials occurred simultaneously (favourable s-ITD). At unfavourable s-ITDs, the discharge rates usually fell below unilateral levels. GABA had contrary effects on the s-ITD functions depending on the drug concentration. A low GABA dose enhanced excitability at favourable s-ITD, but not at unfavourable s-ITDs. In contrast, higher GABA concentrations diminished excitability. Moderate GABA concentrations had no consistent effect. These results suggest that the GABAergic input to NL will either increase or decrease the excitability of the NL neuron depending on the degree to which this GABAergic input is activated. A gain control hypothesis is presented in which the GABAergic input makes ITD processing in NL independent of the stimulus intensity by adjusting the excitability of NL neurons.