Influence of cadmium on oxidative stress and NADH oscillations in mussel mitochondria.

Biological organisms evolved to take advantage of recurring environmental factors which enabled them to assimilate and process metabolic energy for survival. Mitochondria display non-linear oscillations in NADH levels (i.e. wave behavior) that result from the balance between NADH production (aerobic glycolysis) and oxidation for ATP synthesis. The purpose of this study was to examine the effects of cadmium (Cd) on mitochondrial NADH oscillations in quagga mussels Dreissena bugensis exposed to 50 and 100 µg/L CdCl2 for 7 days at 15 °C. Metallothionein (MT) levels, thioredoxin reductase (TrxR) activity and NADH oxidation rate were also determined, as were oscillations in NADH and the formation of dissipative structures (turbidity), in isolated mitochondria suspensions. The results show that exposure to Cd readily induced MT levels at both concentrations tested and that TrxR and NADH oxidase activity was induced at 100 µg/L Cd only. In control mussels, NADH levels oscillated in mitochondria suspensions with a natural period of 2 to 2.5 min for up to 40 min. Exposure to Cd increased the complexity of the frequency profile of NADH oscillations and reduced the amplitudes of the natural signal with a period of 2 to 2.5 min. The formation of dissipative structures decreased in response to a Cd concentration of 100 µg/L but increased at a level of 50 µg/L. The amplitudes at the natural frequency were significantly correlated with NADH oxidase activity (r = -0.91) and with the formation of dissipative structures (r = -0.59). We conclude that Cd could alter the natural frequency in oscillations of NADH in mitochondria, thereby contributing to an increase in NADH oxidation rate and disruption of the spatial organization of mitochondria in suspension. In conclusion, changes in the wave behavior of NADH in mitochondria are proposed as a novel biomarker of toxicity in aquatic organisms.

Primary and secondary prevention of cardiovascular disease in patients with hyperlipoproteinemia (a).

General lipoprotein (Lp) (a) screening can help to identify patients at high risk for cardiovascular disease. Non-invasive methods allow early detection of clinically asymptomatic incipient atherosclerotic disease. Medical treatment options are still unsatisfactory. Lp(a) apheresis is an established treatment in Germany for secondary prevention of progressive cardiovascular disease. Statin-based lowering of LDL cholesterol and thrombocyte aggregation inhibitors still represent the basis of medical treatment. Target levels for LDL-cholesterol should be modified in patients with hyperlipoproteinemia (a).

Indications for apheresis as an ultima ratio treatment of refractory hyperlipidemias.

Lipid apheresis is at present well established in routine treatment of diverse hyperlipoproteinemias refractory to conventional dietary and medical regimens, especially in countries with high medical and socioeconomic standards. Severe familial hypercholesterolemia with atherosclerotic vessel disease involving the coronary arteries is the most frequent indication for lipid apheresis as well as homozygous familial hypercholesterolemia before the development of cardiovascular complications.In hyperlipoproteinemia (a) with progressive vessel disease, lipid apheresis is regularly accepted in Germany. The indication of apheresis in Refsum's disease and the chylomicronemia syndrome is described.

Exclusion of mutations in the gene for type III collagen (COL3A1) as a common cause of intracranial aneurysms or cervical artery dissections: results from sequence analysis of the coding sequences of type III collagen from 55 unrelated patients.

We performed detailed DNA sequencing analysis on type III collagen cDNA from 58 patients with either intracranial artery aneurysms or cervical artery dissections. The 58 patients were of seven different nationalities; among the patients were three pairs of relatives, so that 55 were unrelated, and of these, 29 had at least one blood relative with either an intracranial artery aneurysm or a cervical artery dissection. The age of the patients at the time of diagnosis ranged from 15 to 68 years (mean +/- SD = 40.3 +/- 11.0). The study group consisted of 25 males and 33 females. The analysis covered 3,232 nucleotides of significant (nonredundant) sequences per allele; therefore, we analyzed as many as 355,520 nucleotides. Mutations in the coding sequences for the triple-helical domain of type III collagen were excluded in 40 individuals with intracranial aneurysms and 18 individuals with cervical artery dissections. Direct sequencing of polymerase chain reaction products allowed mutations to be excluded with a high degree of confidence. Mutations that markedly decreased expression from one allele were also excluded in 42 of the 58 individuals, since the presence of both bases at one or more polymorphic sites in the 42 patients showed that two alleles were transcribed. The results indicated that mutations in the gene for type III procollagen (COL3A1) are not a common cause of either intracranial artery aneurysms or cervical artery dissections.

Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms.

Detailed DNA sequencing of the triple-helical domain of type III procollagen was carried out on cDNA prepared from 54 patients with aortic aneurysms. The 43 male and 11 female patients originated from 50 different families and five different nationalities. 43 patients had at least one additional blood relative who had aneurysms. Five overlapping asymmetric PCR products, covering all the coding sequences of the triple-helical domain of type III procollagen, were sequenced with 28 specific sequencing primers. Analysis of the sequencing gels revealed only two nucleotide changes that altered the structure of the protein. One was a substitution of threonine for proline at amino acid position 501 and its functional importance was not clearly established. The other was a substitution of arginine for an obligatory glycine at amino acid position 136. In 40 of the 54 patients, detection of a polymorphism in the mRNA established that both alleles were expressed. The results indicate that mutations in type III procollagen are the cause of only about 2% of aortic aneurysms.