Cardiovascular diseases and the nitric oxide pathway

Fifteen years after its discovery, NO has fully reached an established position in physiology, medicine and therapeutics. It is difficult to find a biological function or a pathological condition where NO does not play a relevant role. Discoveries in the NO field have historically evolved from cardiovascular research, although its influences have already covered nearly all the medical specialties. This review analyzes, step by step, the pathway through which NO is synthesized in the cells of the cardiovascular system and the main physiological and pathological routes it undergoes once it is released. We focus on various diseases affecting the cardiovascular system (atherosclerosis, hypertension, diabetes mellitus and septic shock). We describe in detail those steps of the NO pathway in which anomalies have been detected and may account for the pathophysiology of these diseases. In atherosclerosis, hypertension and diabetes mellitus, the endothelial form of NOS is upregulated, but is very sensitive to environmental conditions, such as substrate or cofactor deficiencies or increases in LDL or glucose. In this situation NOS synthesizes superoxide anion instead of NO leading to oxidative and nitrosative stress. In diabetes mellitus and, very importantly, in septic shock, the inducible form of NOS is highly upregulated. Overproduction of NO appears to underlie the hypotension and tissue damage of septicemia and the destruction of beta-cells in diabetes mellitus. New knowledge of the role of NO in these diseases has started to influence therapeutic design. We also review the current status of research on NO-based therapies.     

Neuropsychologic differences between bilateral dyskinetic and spastic cerebral palsy

This study compared the neuropsychologic performance of 30 adolescents and adults with bilateral dyskinetic, mixed, and spastic cerebral palsy aged between 16 and 38 years. The sample was relatively homogeneous in terms of motor severity; no patients were able to walk unaided. In all subjects, we evaluated the general function of nonverbal reasoning and the following specific neuropsychologic areas: language, visual perception, memory, praxis, and frontal functions. Individuals with dyskinetic cerebral palsy had better auditory comprehension, visuospatial abilities, immediate visual memory, and working verbal memory than those with spastic cerebral palsy. Frontal function was the only cognitive function on which subjects with dyskinetic cerebral palsy had lower scores. We conclude that the neuropsychologic profiles of dyskinetic and spastic cerebral palsy are different.     

The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients

The European Cancer Anaemia Survey (ECAS) was conducted to prospectively evaluate the prevalence, incidence and treatment of anaemia (haemoglobin <12.0 g/dL) in European cancer patients, including the relationship of mild, moderate and severe anaemia to performance status. Patients were evaluated for up to 6 months. Data (N=15367) included demographics, tumour type, performance status, haemoglobin levels, cancer treatments and anaemia treatments. Prevalence of anaemia at enrollment was 39.3% (haemoglobin <10.0 g/dL, 10%), and 67.0% during the survey (haemoglobin <10.0 g/dL, 39.3%). Low haemoglobin levels correlated significantly with poor performance status. Incidence of anaemia was 53.7% (haemoglobin <10.0 g/dL, 15.2%). Anaemia was treated in 38.9% of patients (epoetin, 17.4%; transfusion, 14.9%; and iron, 6.5%). Mean haemoglobin to initiate anaemia treatment was 9.7 g/dL. Anaemia prevalence and incidence in cancer patients are high. Anaemia significantly correlates with poor performance status and many anaemic patients are not treated.     

Medial temporal MR spectroscopy is related to memory performance in normal adolescent subjects

In addition to the study of pathological conditions, magnetic resonance spectroscopy can provide useful information about brain-behavior relationships in normal subjects. Recently, there have been reports of correlations between N-acetylaspartate (NAA) values and cognitive functions in normal adults. We tested the possible specific relationship between the NAA/choline (Cho) ratio in the medial temporal lobe and memory performance in normal adolescents. The medial temporal NAA/Cho ratio was unrelated to age, gender and general intelligence but presented a clear correlation with several memory measures. In the regression analysis two memory variables (RAVLT learning and a face-name recognition task) explained 55.6% of NAA/Cho variance. We conclude that NAA values in the medial temporal lobe are related to memory abilities but not to global intelligence in normal adolescent subjects.     

Comparative evaluation of cytotoxicity and phototoxicity of mono and diacylglycerol amino acid-based surfactants

Extensive efforts have been made, recently, to find surfactants with lower irritancy potential than those presently commercially employed in pharmaceutical and cosmetic preparations. Cytotoxic and phototoxic effects of novel mono and diacylglycerol amino acid-based surfactants (glutamic acid, or arginine) were evaluated.All tested surfactants showed a clear concentration–response relationship to two immortalized cell lines, murine fibroblast cell line, 3T3, and one human keratinocyte cell line, HaCaT, demonstrated by and decrease of NR uptake. Concentrations resulting in 50% inhibition of NR uptake (IC₅₀) range from 30 to 300 μg mL⁻¹.The potential phototoxicity which could result in irritant products, was determined by modulated cytotoxicity via the resazurin reduction to resorufin and neutral red uptake (NRU) endpoints. Surfactants with two chains showed, in general, less cytotoxic but higher phototoxic effect than surfactants with only one chain.