Growth factors decrease in subjects with mild to moderate Alzheimer's disease (AD): potential correction with dehydroepiandrosterone-sulphate (DHEAS).

The integrity of neuroprotection is an important component against the development of cognitive disorders and AD. Within this context, DHEAS would seem to have some positive metabolic and endocrine effects to delay brain aging by recovering the impairment of neuroprotective growth factors. In the present study we measured by ELISA the secretion of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and transforming growth factor-beta1 (TGFbeta1) in the supernatants of cultured circulating peripheral blood mononuclear cells (PBMC) from which natural killer cells (NK) were separated (PBMC-NK) (pg/ml/7.75x10(6) cells) in healthy subjects and in age-matched patients with mild to moderate AD. The growth factors were measured in spontaneous conditions and after stimulation with growth hormone (GH) 1 microg/ml (IGF-1), lipopolysaccharide (LPS) 1 microg/ml (VEGF) and glucose 10 microM (TGF(beta1). AD group demonstrated at baseline a severe reduction of IGF-1 (3.7+1.2 pg/ml after GH), VEGF (63+/-18 pg/ml spontaneous and 210+/-65 pg/ml after LPS) and TGF(beta1 (33+/-10 pg/ml spontaneous and 75+/-12 pg/ml after glucose) secretions compared to healthy elderly subjects (IGF-1, 9.5+/-2.8 pg/ml after GH, p<0.001; VEGF, 117+/-38 pg/ml spontaneous, p<0.001 and 690+/-120 pg/ml after LPS, p<0.001; and TGF(beta1, 73+/-21 pg/ml spontaneous, p<0.001 and 169+/-53 pg/ml after glucose, p<0.001). Significant positive correlations between IGF-1 and VEGF concentrations were found both in healthy subjects (r=0.87, p<0.001) and in AD subjects (r=0.87, p<0.001). The co-incubation of NK cells with DHEAS (10(6) M/ml/cells) significantly increase IGF-1, VEGF and TGF (beta1 production, reaching in AD group the normal concentrations found in healthy subjects (IGF-1, 7.9 + 2.4 pg/ml after GH; VEGF, 105+/-31 pg/ml spontaneous and 670+/-112 pg/ml after LPS; and TGFfbeta1, 68+/-18 pg/ml spontaneous and 155+/-48 pg/ml after glucose). These data suggested that DHEAS is able to increase the immunoendocrine production of neuroprotective growth factors, which is reduced in AD subjects, so suggesting a new approach in the treatment of dementia.

Low nitric oxide values associated with low levels of zinc and high levels of cardiac necrosis markers detected in the plasma of rabbits treated with L-NAME.

Nitric oxide plays a key role as a vasodilating agent and its deficiency is associated with ischemic heart diseases. The aim of this study was to induce biochemical alterations associated with ischemic heart lesions by blocking nitric oxide synthase. L-NAME, a nitric oxide synthase inhibitor, was administered to rabbits and its effects on blood pressure, plasma levels of nitric oxide, zinc and cardiac necrosis markers, heart histology, and electrocardiographic profile were examined. L-NAME administration reduced the nitric oxide levels and consequently increased the diastolic blood pressure. It also caused small areas of myocardial coagulative necrosis, whose dispersed nature made it undetectable by electrocardiograph, and decreased the plasma levels of zinc, which is involved in the enzymatic activities that remove the peroxides damaging the myocardium. This model is proposed for the development of drugs affecting nitric oxide levels with the aim of controlling coronary ischemia.

[Use of intra- and peri-articular peroxide dismutase in clinical orthopedic practice]. / L'uso dei perossido-dismutasi per via endo- e peri-articolare nella pratica clinica ortopedica.

The authors report the results of intra- and peri-articular orgotein treatment in 30 arthritic patients. The patients were examined before, during and at the end of the course of treatment and showed substantial improvement. Negative and mediocre results were more frequent in cases of gonarthrosis. This finding may be accounted for by the severity of the articular situation in these patients, though orgotein treatment is also preferred in such cases, as it avoids iatrogenic damage. The authors also make it clear that no benefit can be achieved by combining the use of local anaesthetics with the orgotein treatment.

Observations on the molecular components stabilizing the microtubular system of the marginal band in the newt erythrocyte.

Microtubules have been classified as either stable or labile, according to their resistance towards depolymerizing agents. The highest stability belongs to those organized in composite structures, in which many other proteins are associated with the tubulin. Among these microtubular systems, the marginal band of amphibian erythrocytes is unusually stable. This system can be readily isolated from Triturus red blood cells, and therefore lends itself very readily to ultrastructural and biochemical analyses. Immunofluorescence and electrophoretic analyses of the isolated bands reveal 14 components, among which tubulin, actin, myosin and a 90K glycoprotein were identified. Tannic acid-glutaraldehyde fixation reveals a conspicuous opaque material surrounding the microtubules. Cationized ferritin binding suggests the presence of anionic sites. Moreover, neuraminidase causes the disorganization of the microtubule-associated opaque material. The 90K glycoprotein is presumed to be related to the unusual stability of the microtubular system forming the marginal band.