Selective COX-2 inhibitors and risk of myocardial infarction

Selective inhibitors of cyclooxygenase- 2 ( COX- 2, ` coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non- steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myocardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/ parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX- 2 on the cardiovascular system. Although COX- 2, in contrast to the cyclooxygenase-1 ( COX- 1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX- 2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX- 2- dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin ( PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX- 2, and its levels are reduced to less than half of normal when COX- 2 is inhibited. This review outlines the rationale for the development of selective COX- 2 inhibitors and the pathophysiological consequences of selective inhibition of COX- 2 with special regard to vasoactive prostaglandins. It describes coxibs that are currently available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright (C) 2005 S. Karger AG, Basel

Blindness incidence in Germany - A population-based study from Württemberg-Hohenzollern

Few data on the incidence of blindness in Germany are available. We analysed causes of legal blindness for the region Württemberg-Hohenzollern (population 5.5 million) in order to help fill in this gap. Material and Methods: Population-based investigation on the incidence of legal blindness (visual acuity <1/50) based on materials from the social servies. Age-dependent blindness incidences were modelled via logistic regression models. Results: 647 blind persons were newly registered in 1994 (blindness incidence 11.6/100,000). The blindness incidence is moderate in infants (4.5/100,000) and decreases further during childhood. At the age of 20 years, the incidence again rises to the former level and remains relatively constant. After the age of 60 years, the incidence increases sharply: 5-year odds ratios are 1.76 (CI: 1.68-1.85) in women and 1.72 (CI: 1.60-1.84) in men. The blindness incidence is higher in women, 15.6/100,000, compared to 12.2/100,000 in men. The major causes of blindness are: macular degeneration, 3.92/100,000; diabetic retinopathy, 2.01/100,000; glaucoma, 1.6/100,000; high myopia, 0.77/100,000; optic atrophy, 0.68/100,000; central nervous system-triggered blindness; 0.56/100,000, and tapetoretinal degenerations, 0.52/100,000. Discussion: Due to monetary incentives for the blind persons, social service files offer accurate and complete data. Besides macular degeneration, glaucoma and dia betic retinopathy are major causes of blindness. Thus, this study suggests further blindness prevention activities for diabetic retinopathy and glaucoma

Microscopic Evidence of Spin State Order and Spin State Phase Separation in Layered Cobaltites RBaCo2O5.5 with R=Y, Tb, Dy, and Ho

We report muon spin relaxation measurements on the magnetic structures of RBaCo_2O_5.5 with R=Y, Tb, Dy, and Ho. Three different phases, one ferrimagnetic and two antiferromagnetic, are identified below 300 K. They consist of different ordered spin state arrangements of high-, intermediate-, and low-spin Co^3+ of CoO_6 octahedra. Phase separation into well separated regions with different spin state order is observed in the antiferromagnetic phases. The unusual strongly anisotropic magnetoresistance and its onset at the FM-AFM phase boundary is explained.Comment: 4 pages, accepted for publication in Phys. Rev. Let

Electronic structure of the molecule based magnet Cu PM(NO3)2 (H2O)2

We present density functional calculations on the molecule based S=1/2 antiferromagnetic chain compound Cu PM(NO3)2 (H2O)2; PM = pyrimidine. The properties of the ferro- and antiferromagnetic state are investigated at the level of the local density approximation and with the hybrid functional B3LYP. Spin density maps illustrate the exchange path via the pyrimidine molecule which mediates the magnetism in the one-dimensional chain. The computed exchange coupling is antiferromagnetic and in reasonable agreement with the experiment. It is suggested that the antiferromagnetic coupling is due to the possibility of stronger delocalization of the charges on the nitrogen atoms, compared to the ferromagnetic case. In addition, computed isotropic and anisotropic hyperfine interaction parameters are compared with recent NMR experiments

Dzyaloshinsky-Moriya Spin Canting in the LTT Phase of La2-x-yEuySrxCuO4

The Cu spin magnetism in La2-x-yEuySrxCuO4 (x<=0.17; y<=0.2) has been studied by means of magnetization measurements up to 14 T. Our results clearly show that in the antiferromagnetic phase Dzyaloshinsky-Moriya (DM)superexchange causes Cu spin canting not only in the LTO phase but also in the LTLO and LTT phases. In La1.8Eu0.2CuO4 the canted DM-moment is about 50% larger than in pure La2CuO4 which we attribute to the larger octahedral tilt angle. We also find clear evidence that the size of the DM-moment does not change significantly at the structural transition at T_LT from LTO to LTLO and LTT. The most important change induced by the transition is a significant reduction of the magnetic coupling between the CuO2 planes. As a consequence, the spin-flip transition of the canted Cu spins which is observed in the LTO phase for magnetic field perpendicular to the CuO2 planes disappears in the LTT phase. The shape of the magnetization curves changes from the well known spin-flip type to a weak-ferromagnet type. However, no spontaneous weak ferromagnetism is observed even at very low temperatures, which seems to indicate that the interlayer decoupling in our samples is not perfect. Nonetheless, a small fraction (<15%) of the DM-moments can be remanently magnetized throughout the entire antiferromagnetically ordered LTT/LTLO phase, i.e. for T<T_LT and x<0.02. It appears that the remanent DM-moment is perpendicular to the CuO2 planes. For magnetic field parallel to the CuO2 planes we find that the critical field of the spin-flop transition decreases in the LTLO phase, which might indicate a competition between different in-plane anisotropies. To study the Cu spin magnetism in La2-x-yEuySrxCuO4, a careful analysis of the Van Vleck paramagnetism of the Eu3+ ions was performed.Comment: 22 pages, 27 figure

High temperature ferromagnetism of Li-doped vanadium oxide nanotubes

The nature of a puzzling high temperature ferromagnetism of doped mixed-valent vanadium oxide nanotubes reported earlier by Krusin-Elbaum et al., Nature 431 (2004) 672, has been addressed by static magnetization, muon spin relaxation, nuclear magnetic and electron spin resonance spectroscopy techniques. A precise control of the charge doping was achieved by electrochemical Li intercalation. We find that it provides excess electrons, thereby increasing the number of interacting magnetic vanadium sites, and, at a certain doping level, yields a ferromagnetic-like response persisting up to room temperature. Thus we confirm the surprising previous results on the samples prepared by a completely different intercalation method. Moreover our spectroscopic data provide first ample evidence for the bulk nature of the effect. In particular, they enable a conclusion that the Li nucleates superparamagnetic nanosize spin clusters around the intercalation site which are responsible for the unusual high temperature ferromagnetism of vanadium oxide nanotubes.Comment: with some amendments published in Europhysics Letters (EPL) 88 (2009) 57002; http://epljournal.edpsciences.or