Crop Economics for Ohio

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Different behaviour of the N-terminal and C-terminal fragment of proatrial natriuretic factor in plasma of healthy subjects as well as of patients with cirrhosis

N-terminal (atrial natriuretic factor (ANF) 1-98) and C-terminal (ANF 99-126) fragments of proatrial natriuretic factor (NTA and CTA, respectively) were determined in plasma of healthy subjects adopting different postures and in patients with cirrhosis. Seven healthy subjects were investigated while seated and 30 min after assuming a horizontal position. NTA plasma concentrations increased in subjects in the horizontal position (from 734±250 (SE) fmol/ml to 9021227 fmol/ml; p<0.05). In contrast, CTA plasma concentrations remained unchanged (9.2+1.3 fmol/ml vs 8.9±1.6 fmol/ml). In 10 patients with cirrhosis of the liver, NTA concentrations were markedly (p<0.001) elevated compared to 11 healthy subjects (2334±291 fmol/ml vs 743±155 fmol/ml). However, there was no difference of CTA plasma levels between cirrhotic patients and healthy subjects (8.7±1.3 fmol/ml vs 8.2±0.9 fmol/ml). These data demonstrate changes of the plasma concentration of the N-terminal fragment of proatrial natriuretic factor by posture and in liver disease, in contrast to unchanged levels of the C-terminal fragment

A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.

Background and aims: The transcription factor nuclear factor kappa B (NF-kB) has risen as a promising target for anti-inflammatory therapeutics. In the liver, however, NFkB inhibition mediates both damaging and protective effects. The outcome is deemed to depend on the liver cell type addressed. Recent gene knock-out studies focused on the role of NF-kB in hepatocytes, whereas the role of NF-kB in Kupffer cells has not yet been investigated in vivo. Here we present a novel approach, which may be suitable for clinical application, to selectively target NF-kB in Kupffer cells and analyse the effects in experimental models of liver injury. Methods: NF-kB inhibiting decoy oligodeoxynucleotides were loaded upon gelatin nanoparticles (D-NPs) and their in vivo distribution was determined by confocal microscopy. Liver damage, NF-kB activity, cytokine levels and apoptotic protein expression were evaluated after lipopolysaccharide (LPS), D-galactosamine (GalN)/LPS, or concanavalin A (ConA) challenge and partial warm ischaemia and subsequent reperfusion, respectively. Results: D-NPs were selectively taken up by Kupffer cells and inhibited NF-kB activation. Inhibition of NF-kB in Kupffer cells improved survival and reduced liver injury after GalN/LPS as well as after ConA challenge. While anti-apoptotic protein expression in liver tissue was not reduced, pro-apoptotic players such as cJun N-terminal kinase (JNK) were inhibited. In contrast, selective inhibition of NF-kB augmented reperfusion injury. Conclusions: NF-kB inhibiting decoy oligodeoxynucleotide- loaded gelatin nanoparticles is a novel tool to selectively inhibit NF-kB activation in Kupffer cells in vivo. Thus, liver injury can be reduced in experimental fulminant hepatitis, but increased at ischaemia–reperfusion

Investigations on Tetragonally Distorted Sodium Thallide NaTl‐tI8

In-depth investigations of the long-time known Zintl phase NaTl revealed a phase transition of tetragonal NaTl-tI8 [I4(1)/amd; a = 5.2268(9) angstrom, c = 7.539(1) angstrom, V = 205.97(9) angstrom(3)] to Zintl's cubic NaTl-cF16 [Fd3m; a = 7.4697(6) angstrom, V = 416.79(5) angstrom(3)] between 351 and 355 K. This phase transformation was observed for NaTl prepared by two different synthetic routes including Zintl's original procedure. An excess of sodium applied during the synthesis in liquid ammonia also resulted in the formation of NaTl-tI8. DSC measurements suggest a first order phase transition. In addition to in-situ temperature dependent powder X-ray diffraction experiments, DSC measurements and solid-state NMR investigations, we also performed theoretical DOS and band structure calculations for the cubic and tetragonal phase, respectively. The results suggest Na-Tl interactions in the second coordination sphere being responsible for the observed tetragonal distortion of Zintl's cubic NaTl

Atrial Natriuretic Peptide Protects against Histamine-Induced Endothelial Barrier Dysfunction in Vivo

Endothelial barrier dysfunction is a hallmark of many severe pathologies, including sepsis or atherosclerosis. The cardiovascular hormone atrial natriuretic peptide (ANP) has increasingly been suggested to counteract endothelial leakage. Surprisingly, the precise in vivo relevance of these observations has never been evaluated. Thus, we aimed to clarify this issue and, moreover, to identify the permeability-controlling subcellular systems that are targeted by ANP. Histamine was used as important pro-inflammatory, permeability-increasing stimulus. Measurements of fluorescein isothiocyanate (FITC)-dextran extravasation from venules of the mouse cremaster muscle and rat hematocrit values were performed to judge changes of endothelial permeability in vivo. It is noteworthy that ANP strongly reduced the histamine-evoked endothelial barrier dysfunction in vivo. In vitro, ANP blocked the breakdown of transendothelial electrical resistance (TEER) induced by histamine. Moreover, as judged by immunocytochemistry and Western blot analysis, ANP inhibited changes of vascular endothelial (VE)-cadherin, β-catenin, and p120ctn morphology; VE-cadherin and myosin light chain 2 (MLC2) phosphorylation; and F-actin stress fiber formation. These changes seem to be predominantly mediated by the natriuretic peptide receptor (NPR)-A, but not by NPR-C. In summary, we revealed ANP as a potent endothelial barrier protecting agent in vivo and identified adherens junctions and the contractile apparatus as subcellular systems targeted by ANP. Thus, our study highlights ANP as an interesting pharmacological compound opening new therapeutic options for preventing endothelial leakage

Complete shutdown of microvascular perfusion upon hepatic cryothermia is critically dependent on local tissue temperature

Since microvascular dysfunction with complete circulatory arrest and, thus, prolongation of tissue ischaemia is considered a potential mechanism for cell necrosis following hepatic cryosurgery, we determined the temperature necessary for induction of complete nutritive perfusion failure in cryothermia-treated rat livers. After localization of the cryoprobe with seven thermocouples and application of a single or double freeze–thaw cycle, in vivo fluorescence microscopy of the cryoinjured left lobe was performed over a 2-h period using a computer-controlled stepping motor, which guaranteed analysis of the identical liver tissue segments with exact allocation of the thermocouples and thus determination of tissue temperature. Cryothermia resulted in a central non-perfused part of injury, surrounded by a heterogeneously perfused peripheral zone. The non-perfused area after single and double freezing continuously increased over the first 90-min period due to a successive shutdown of perfusion within the peripheral border zone. Analysis of the thermocouples' temperature at the end of freezing revealed the 0°C-front at 11.7 mm (single freeze–thaw cycle) and 12.1 mm (double freeze–thaw cycle) distant from the centre of the cryoprobe, which exactly corresponds with the initial (30 min) expansion of the area with nutritive perfusion failure. The increased non-perfused tissue area at 2 h conformed a critical border temperature between 8.29 ± 1.63°C and 9.07 ± 0.24°C. From these findings, we conclude that freezing of liver tissue to temperatures of at least < 0°C causes complete/irreversible perfusion failure, which consequently will result in cell death and tissue necrosis, and may thus be supposed as a prerequisite for the safe and successful application of cryosurgery in hepatic tumour ablation. © 2000 Cancer Research Campaig

Flavopiridol Protects Against Inflammation by Attenuating Leukocyte-Endothelial Interaction via Inhibition of Cyclin-Dependent Kinase 9

Objective: The cyclin-dependent kinase (CDK) inhibitor flavopiridol is currently being tested in clinical trials as anticancer drug. Beyond its cell death–inducing action, we hypothesized that flavopiridol affects inflammatory processes. Therefore, we elucidated the action of flavopiridol on leukocyte–endothelial cell interaction and endothelial activation in vivo and in vitro and studied the underlying molecular mechanisms. Methods and Results: Flavopiridol suppressed concanavalin A–induced hepatitis and neutrophil infiltration into liver tissue. Flavopiridol also inhibited tumor necrosis factor-α–induced leukocyte– endothelial cell interaction in the mouse cremaster muscle. Endothelial cells were found to be the major target of flavopiridol, which blocked the expression of endothelial cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin), as well as NF-κB-dependent transcription. Flavopiridol did not affect inhibitor of κB (IκB) kinase, the degradation and phosphorylation of IκBα, nuclear translocation of p65, or nuclear factor-κB (NF-κB) DNA-binding activity. By performing a cellular kinome array and a kinase activity panel, we found LIM domain kinase-1 (LIMK1), casein kinase 2, c-Jun N-terminal kinase (JNK), protein kinase Cθ (PKCθ), CDK4, CDK6, CDK8, and CDK9 to be influenced by flavopiridol. Using specific inhibitors, as well as RNA interference (RNAi), we revealed that only CDK9 is responsible for the action of flavopiridol. Conclusion: Our study highlights flavopiridol as a promising antiinflammatory compound and inhibition of CDK9 as a novel approach for the treatment of inflammation-associated diseases

Feasibility of multimodal 3D neuroimaging to guide implantation of intracranial EEG electrodes

Since intracranial electrode implantation has limited spatial sampling and carries significant risk, placement has to be effective and efficient. Structural and functional imaging of several different modalities contributes to localising the seizure onset zone (SoZ) and eloquent cortex. There is a need to summarise and present this information throughout the pre/intra/post-surgical course

Bounded Languages Meet Cellular Automata with Sparse Communication

Cellular automata are one-dimensional arrays of interconnected interacting finite automata. We investigate one of the weakest classes, the real-time one-way cellular automata, and impose an additional restriction on their inter-cell communication by bounding the number of allowed uses of the links between cells. Moreover, we consider the devices as acceptors for bounded languages in order to explore the borderline at which non-trivial decidability problems of cellular automata classes become decidable. It is shown that even devices with drastically reduced communication, that is, each two neighboring cells may communicate only constantly often, accept bounded languages that are not semilinear. If the number of communications is at least logarithmic in the length of the input, several problems are undecidable. The same result is obtained for classes where the total number of communications during a computation is linearly bounded