Classic NSAID and selective cyclooxygenase (COX)-1 and COX-2 inhibitors in healing of chronic gastric ulcers

Prostaglandins (PG) derived from COX-1 are essential for the maintenance of mucosal integrity but COX-2 isoform synthesizes PG at a site of inflammation. Recently, COX-2 mRNA expression was demonstrated at the ulcer edge during healing of chronic gastric ulcers but the role for expression of COX-2 and its products such as PGE(2) and cytokines including interleukin (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in ulcer healing remains unknown. In this study, Wistar rats with gastric ulcers produced by serosal application of acetic acid (ulcer area 28 mm(2)) received daily treatment either with: (1) vehicle (saline); (2) NS-398 (10 mg/kg-d i.g.) and Vioxx (5 mg/kg-d i.g.), both, highly specific COX-2 inhibitors; (3) meloxicam (5 mg/kg-d i.g.), a preferential inhibitor of COX-2; (4) resveratrol (10 mg/kg-d i.g.), a specific COX-1 inhibitor; (5) indomethacin (5 mg/kg-d i.g); and (6) aspirin (ASA; 50 mg/kg-d i.g.), non-selective inhibitors of both COX-1 and COX-2. At day 3, 7, and 14 after ulcer induction, the animals were sacrificed and the area of gastric ulcers was determined by planimetry and histology, gastric blood flow (GBF) at ulcer base and margin was measured by H(2) clearance technique, and blood was withdrawn for measurement of plasma IL-1beta and TNFalpha levels. The mucosal biopsy samples were taken for the determination of PGE(2) generation by RIA and expression of COX-1, COX-2, IL-1beta, and TNFalpha mRNA by RT-PCR. In vehicle-treated rats, gastric ulcers healed progressively and at day 14 the healing was completed, accompanied by a significant rise in the GBF at ulcer margin. The IL-1beta, TNFalpha, and COX-1 mRNA were detected in intact and ulcerated gastric mucosa, whereas COX-2 mRNA were upregulated only in ulcerated mucosa with peak observed at day 3 after ulcer induction. The plasma IL-1beta level was significantly increased at day 3 and 7 but then declined at day 14 to that measured in vehicle-controls. Indomethacin and ASA, which suppressed PGE(2) generation both in the non-ulcerated and ulcerated gastric mucosa, significantly delayed the rate of ulcer healing and this was accompanied by the fall in GBF at ulcer margin and further elevation of plasma IL-1beta and TNFalpha levels, which was sustained up to the end of the study. Treatment with NS-398 and Vioxx, which caused only a moderate decrease in the PGE(2) generation in the non-ulcerated gastric mucosa, delayed ulcer healing and attenuated significantly the GBF at ulcer margin and PGE(2) generation in the ulcerated tissue, while raising the plasma IL-1beta and TNFalpha similarly to those observed in indomethacin- and ASA-treated rats. Resveratrol, which suppressed the PGE(2) generation in both non-ulcerated and ulcerated gastric mucosa, prolonged ulcer healing and this was accompanied by the fall in the GBF at the ulcer margin and a significant increase in plasma IL-1beta and TNFalpha levels. We conclude that (1) classic NSAID delay ulcer healing due to suppression of endogenous PG, impairment in GBF at ulcer area, and excessive cytokine expression and release, and (2) this deleterious effect of classic NSAID on the healing of pre-existing ulcers can be reproduced by selective COX-1 and COX-2 inhibitors, suggesting that both COX isoforms are important sources of PG that appear to contribute to ulcer healing.     

Origin of Violet‐Blue Emission in Ti‐Doped Gahnite

ZnAl₂O₄ doped with Ti⁴⁺ (2%) was synthesized by the hydrothermal method at 220°C at pressure of 25 bars. An average grain size of the as‐prepared sample was 3 nm, the samples with biggest grain size were obtained after annealing at 300°C, 500°C, 600°C, 700°C, and 900°C, diameter of the latter was about 33 nm. IR spectroscopy indicated that ZnAl₂O₄ was partially inverted. The degree of the inversion decreases with increase in the annealing temperature but increases with increasing Ti⁴⁺ content. Absorption and emission spectra as well as emission decay profiles were recorded at 300 and 77 K. The observed spectra are due to charge‐transfer O^2??Ti⁴⁺ transitions. Color of the emission depends on the nanocrystal size and with increase in its diameter changes from violet to blue, accordingly the absorption bands exhibit redshift. The calculations based on Density Functional Theory confirmed the experimental results. 3d electrons of titanium ions form the bottom of the ZnAl₂O₄:Ti⁴⁺ conduction band, oxygen, aluminum or zinc vacancies create additional levels in the gahnite energy band gap. It was also found that in ZnAl₂O₄ aluminum or zinc vacancy induces magnetism with relatively high magnetic moment close to 1 μ_B per vacancy.     

Ein neues integrales Verfahren zur Quantifizierung der Grundwasserimmission, Teil II: Numerische L?sung und Anwendung in Eppelheim

Im ersten Beitrag zu diesem Thema ( Teutsch et al. 2000) wurde ein neues Erkundungsverfahren zur Quantifiziuerng der Schadstoffbelastung in Grundwasser an Deponien und Altlasten vorgestellt, das eine Bestimmung der Schadstoffbelastung im natürlichen Str?mungsfeld mit einer hohen Erkundungssicherheit erm?glicht. In diesem zweiten Beitrag wird der erstmalige praktische Einsatz des Verfahrens an einem Feldstandort vorgestellt. Dabei stand die erweiterte, differentielle Immissionsmessung im Vordergrund, die zus?tzlich zur Bestimmung von Gesamt-Schadstofffrachten und mittleren Konzentrationen auch Angaben zur r?umlichen Konzentrationsverteilung entlang definierter Kontrollquerschnitte senkrecht zur Str?mungsrichtung erm?glicht. Neben der allgemeinen Erprobung der Mess- und Auswerteans?tze sollte mit den Messungen insbesondere gezeigt werden, dass das neue Verfahren auch bei geringen Grundwasserschadstoffkonzentrationen einsetzbar ist. Ferner sollte die erreichbare r?umliche Aufl?sung der Konzentrationsverteilung im Abstrom demonstriert werden.     

Investigations on printed elastic resistors containing carbon nanotubes

This paper presents the results of authors investigations on elaboration of a new thick film composition filled with carbon nanotubes (CNTs). The polymer composition consists of polymer vehicle, which is the solution of organic resin in certain combination of solvents, and functional phase—carbon nanotubes well dispersed in the vehicle. The pastes were applied with screen-printing on several substrates and temperature cured. The properties of obtained layers were characterized. Series of samples were prepared with different amount of CNTs to evaluate electrical properties. Changes in resistance were investigated during periodic mechanical and temperature stresses, realized through cyclical bending and rapid temperature change. Tensometric effect was also investigated. Investigations have proved that polymer composites based on carbon nanotubes exhibit high resilience to stress factors. Resistance change in function of temperature was also investigated to evaluate temperature coefficient of resistance (TCR). All this aspects are important for elastic resistors fabrication in printed electronics microcircuits. Resistance and noise measurements in cryostats have also been involved. 1/f type noise has been observed. Noise intensity, calculated in decade frequency bands, rises significantly with increasing temperature. Activation energies of thermally activated noise sources (TANS) have been revealed using low-frequency noise spectroscopy. Relatively large value of negative TCR has been obtained from resistance versus temperature curve. Calculated dimensionless sensitivity is similar to that observed in cryogenic temperature sensors. However, bulk noise intensity of resistive layer is larger than obtained for lead containing RuO₂ based resistive layers.     

Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies

Modulation of N-methyl-D-aspartate receptors in the brain by protein phosphorylation may play a central role in the regulation of synaptic plasticity. To examine the phosphorylation of the NR1 subunit of N-methyl-D-aspartate receptors in situ, we have generated several polyclonal antibodies that recognize the NR1 subunit only when specific serine residues are phosphorylated. Using these antibodies, we demonstrate that protein kinase C (PKC) phosphorylates serine residues 890 and 896 and cAMP-dependent protein kinase (PKA) phosphorylates serine residue 897 of the NR1 subunit. Activation of PKC and PKA together lead to the simultaneous phosphorylation of neighboring serine residues 896 and 897. Phosphorylation of serine 890 by PKC results in the dispersion of surface-associated clusters of the NR1 subunit expressed in fibroblasts, while phosphorylation of serine 896 and 897 has no effect on the subcellular distribution of NR1. The PKC-induced redistribution of the NR1 subunit in cells occurs within minutes of serine 890 phosphorylation and reverses upon dephosphorylation. These results demonstrate that PKA and PKC phosphorylate distinct residues within a small region of the NR1 subunit and differentially affect the subcellular distribution of the NR1 subunit.     

Designing A Business-Justified Intranet Project

The ubiquity of both intranets and success stories about their rich returns on investment may provide solid foundation for their recommendation but does not lessen the need for a disciplined project and evaluation process. Using the methodology presented here for identifying and designing a business-justified intranet project helps minimize egregious errors and ensure the commitment, resources, and interest necessary for long-term success.     

Different patterns of gamma delta and alpha beta T cell redistribution in the mouse after partial gastrectomy

The authors define the current role of femoral osteotomy in the treatment of the sequelae of congenital hip dysplasia (CHD) in the adult in light of the increasing orientation towards prosthetization. They report a personal philosophy on the subject after analyzing the criteria on which are based indications for osteotomy, the various types of osteotomy, the influence of osteotomy on other skeletal regions, the problems of prosthetization on osteotomy, and expectations concerning of the quality of the life of the patients submitted to osteotomy.     

Issues in Distributed it Management

The implementation and management problems facing today's IT operations managers and administrators working with distributed systems and networks are well known. No simple solution exists. Success requires the enterprise to define clearly and explicitly both the problem to be solved and the goal of the project.     

Increased ubiquitin expression suppresses the cell cycle defect associated with the yeast ubiquitin conjugating enzyme, CDC34 (UBC3). Evidence for a noncovalent interaction between CDC34 and ubiquitin

The yeast ubiquitin (Ub) conjugating enzyme CDC34 plays a crucial role in the progression of the cell cycle from the G1 to S phase. In an effort to identify proteins that interact with CDC34 we undertook a genetic screen to isolate genes whose increased expression suppressed the cell cycle defect associated with the cdc34-2 temperature-sensitive allele. From this screen, the poly-Ub gene UBI4 was identified as a moderately strong suppressor. The fact that the overexpression of a gene encoding a single Ub protein could also suppress the cdc34-2 allele indicated that suppression was related to the increased abundance of Ub. Ub overexpression was found to suppress two other structurally unrelated cdc34 mutations, in addition to the cdc34-2 allele. In all three cases, suppression depended on the expression of Ub with an intact carboxyl terminus. Only the cdc34-2 allele, however, could be suppressed by Ub with an amino acid substitution at lysine 48 which is known to be involved in multi-Ub chain assembly. Genetic results showing allele specific suppression of cdc34 mutations by various Ub derivatives suggested a specific noncovalent interaction between Ub and CDC34. Consistent with this prediction, we have shown by chemical cross-linking the existence of a specific noncovalent Ub binding site on CDC34. Together, these genetic and biochemical experiments indicate that Ub suppression of these cdc34 mutations results from the combined contributions of Ub-CDC34 thiol ester formation and a noncovalent interaction between Ub and CDC34 and therefore suggest that the correct positioning of Ub on a surface of the ubiquitin conjugating enzyme is a requirement of enzyme function.     

Rethinking community: Analyzing the landscape of community solar through the community-place nexus

This paper analyzes the framing of community in community solar projects from a geographic perspective. Through an extensive literature review of academic articles, policy documents and research theses, along with analysis of web-based literature from solar developers, utilities, goverment and non-government agencies, this paper provides a critical perspective for enhancing limited research of an emerging community energy framework. We argue the concept of community has not been adequately defined in relation to community solar. Consequently, the concept of community has been misrepresentated through what we define as ‘community washing’.