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Biomedical subjects

A Grasso

Publications and source records attributed to A Grasso.

At least 91 records · Page 5Linked to original sources

[Use of citicoline in the study of chronic cerebrovascular diseases].

Some of the disturbances encountered in patients with chronic cerebral vasculopathies may be attributable to associated or concomitant pathologies such as arterial hypertension. In many of the papers published on citicoline it is less than clear whether the improvement in the symptoms is the result of the treatment of the hypertension or the substance used. In conclusion, the importance of correct treatment of hypertension in order to cure certain standard chronic cerebral vasculopathies is emphasised and the value of citicoline in improving kinesthesis, mnemonic and perceptive-motor efficiency is confirmed.

Adrenergic beta-Antagonists↗

Permeation of divalent cations through alpha-latrotoxin channels in lipid bilayers: steady-state current-voltage relationships.

alpha-Latrotoxin, a polypeptide neurotoxin known to cause massive release of transmitter from vertebrate nerve terminals, is thought to act by forming cation-selective channels in plasma membranes. This paper describes the steady-state current carried by Ca2+, Sr2+ and Ba2+ through pores of alpha-LaTx molecules incorporated in artificial bilayer membranes made of neutral lipids. Even when the solutions separated by the membrane are identical, the I-V relations rectify strongly, the current being higher when the side to which the toxin is added is positive. The polarity of the rectification is consistent with the hypothesis that the mechanism of action of the toxin is, at least in part, that of promoting inwardly directed flow of cations, and thus, accumulation of Ca2+ and other ions in the intracellular spaces. The dependence of the I-V characteristics on voltage and Ca2+ concentration is well described by a one-site, one-ion model for a channel. Three parameters of the model are deduced: the binding constant of the site for Ca2+, K = 1.5 M-1 (or K = 7 M-1 when activities are used instead of concentrations); the "electrical" distance of the site from the toxin-containing solution, alpha = 0.3; the free energy difference between the two barrier peaks, delta F = 0.26 kT. The values of the parameters deduced by studying the channel in the presence of Ca2+ give theoretical curves that also fit the data with Sr2+ and Ba2+, indicating a low level of discrimination among these three cations.

Arthropod Venoms↗

Characterization and some properties of the venom gland extract of a theridiid spider (Steatoda paykulliana) frequently mistaken for black widow spider (Latrodectus tredecimguttatus).

The simplified purification protocol established for the isolation of alpha-latrotoxin from the venom of the spider Latrodectus tredecimguttatus, has been employed for the purification of toxic components present in the venom of the spider Steatoda paykulliana. The venom of this spider, frequently mistaken for L. tredecimguttatus, is by tradition considered to cause an envenomation potentially dangerous to man. The venom of S. paykulliana has little toxic effect on guinea-pigs but is extremely toxic to houseflies (Musca domestica). No proteolytic activity was detectable. Interaction of microgram/ml amounts of the venom extract with artificial lipid membranes produces an increase of membrane conductance through the formation of stable ion-permeable channels modulated by the direction and size of the electric potential differences across the membrane. Higher concentrations of this venom are able to stimulate the release of transmitters from neurosecretory cells in a fashion reminiscent of black widow spider venom. Antibodies against the whole L. tredecimguttatus venom gave a few positive cross-reactions in the immunodiffusion test with S. paykulliana venom gland extract indicating the presence of common molecular sequences in the two venoms. Polyclonal antibodies against alpha-latrotoxin did not cross-react in the immunodiffusion test with S. paykulliana venom extracts, nor in the immunofluorescence assay with its cephalothorax sections, thus suggesting that the venom glands do not contain alpha-latrotoxin. A partial characterization of S. paykulliana venom has been performed and a high molecular weight protein toxic to houseflies has been partially purified.

Animals↗

Effects of Org OD 14 on pituitary and peripheral beta-endorphin in castrated rats and post-menopausal women.

The aim of the first part of this study was to evaluate the effects of a new synthetic steroid (7 alpha,17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14), on anterior pituitary (AP) and neurointermediate pituitary lobe (NIL) contents and on circulating levels of beta-endorphin (beta-EP) in rats. Three weeks after ovariectomy, groups of 9 rats were treated with either Org OD 14 (2 or 10 micrograms/day/rat for 14 days) or a placebo. In addition, 2 groups of ovariectomized rats were also treated with oestradiol benzoate (EB) (2 or 10 micrograms/day/rat for 14 days) to compare the effectiveness of the new steroid with that of a classical oestrogenic substance. beta-Ep concentrations were measured in plasma and in AP and NIL extracts by means of double-antibody radioimmunoassay (RIA), employing a specific anti-camel beta-EP (C-terminal fragment). Both doses of Org OD 14 induced a significant dose-related increase in plasma and pituitary lobe beta-EP concentrations as compared with the results on placebo treatment. By comparison, EB was active only at a dose of 10 micrograms/day. Despite the common stimulatory effects of EB and Org OD 14 on pituitary beta-EP, these findings suggest that the two steroids have different modes of action. The second part of the study investigated the changes in beta-EP and beta-lipotrophin (beta-LPH) plasma levels in a group of post-menopausal women treated for 6 months with Org OD 14 (2.5 mg/day) in comparison with the levels in a placebo-treated group. The clinical efficacy of Org OD 14 treatment in post-menopausal symptoms was confirmed, as well as its lack of or only transient effect on plasma lipids and lipoproteins. beta-EP and beta-LPH plasma levels were significantly higher in the Org OD 14-treated group than in the placebo group as from the second month until the end of the observation period.

Adult↗

A functional domain on the alpha-latrotoxin molecule, distinct from the binding site, involved in catecholamine secretion from PC12 cells: identification with monoclonal antibodies.

Seven monoclonal antibodies (mAbs) have been produced against alpha-latrotoxin (alpha-Latx), the toxin component of black widow spider venom that stimulates release of neurotransmitters from PC12 cells. These mAbs were characterized by an enzyme-linked immunosorbent assay and by neutralization analysis of the secretagogue properties of the toxin. The production of a panel of mAbs, possibly directed against different epitopes of alpha-Latx, provides a useful set of reagents to dissect the molecular regions of the toxin having different functions and to describe steps of its mode of action in responsive cells. Attention was focused on one of these mAbs (4C4.1), which inhibits in a dose-dependent fashion both toxin-stimulated and crude venom stimulated dopamine release from PC12 cells, prevents toxin-induced 45Ca2+ accumulation in PC12, alters toxin-dependent phosphoinositide breakdown, and prevents toxin-induced channel formation in artificial lipid bilayers. Since, within certain experimental conditions, mAb 4C4.1 is able to recognize the toxin bound to cells, we conclude that its effects were not a consequence of a direct interference with binding. On the basis of kinetic analysis of mAb interference on toxin action, expressed as accumulation of inositol phosphates and transmitter secretion, we suggest that the described effects result primarily from the blockade of an event immediately successive to binding and central for the full expression of toxin action. The availability of mAb 4C4.1 now makes possible the molecular characterization of the toxin moiety responsible for such an event.

Adrenal Gland Neoplasms↗

Benefits and risks of different hormonal replacement therapies in post-menopausal women.

A total of 113 women who presented with climacteric symptoms participated in the study. They were randomly allocated to seven groups of 10-27 subjects, who received for 6 mth the following therapies, respectively: conjugated oestrogens (CE) 0.625 mg/day for 21 days + norethisterone (NET) 5 mg/day from day 12 to day 21; CE + cyproterone acetate (CPA) 12.5 mg/day from day 1 to day 10; oestradiol valerate (EV) 2 mg/day for 21 days + NET; EV + CPA; oestriol (E3) 2-4 mg/day; tibolone (ORG OD14) 2.5 mg/day; and placebo, one tablet/day. Hot flushes decreased significantly over the treatment period in all seven groups. However, E3 was less effective at the dose used than CE, EV or ORG OD 14. At the end of the 6 month treatment period histological examination revealed no changes in endometrial morphology in any of the patients treated. Indeed, the addition of a progestogen even induced regression of endometrial hyperplasia in 8 cases. No significant variation in the plasma levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) was observed after the second and sixth months of treatment with E3 or ORG OD 14. After 6 months, treatment with CE/EV + CPA produced a significant increase in HDL, while treatment with CE/EV + NET brought about a reduction in total cholesterol and HDL and an increase in LDL.

Adult↗

Tetanus toxin affects the K+-stimulated release of catecholamines from nerve growth factor-treated PC12 cells.

Tetanus toxin specifically binds to neuronal surfaces and interferes with the release of transmitters. The effect of tetanus toxin pretreatment of PC12 cell line, taken as a model of neuronal cells in culture, was studied and found that it depresses depolarization-dependent catecholamines secretion. This effect is limited to PC12 cells fully differentiated by the action of Nerve Growth Factor (NGF) and is indicative of the expression of specific binding sites for tetanus toxin during transition from the undifferentiated state. Specific binding of [125I] tetanus toxin to NGF-treated PC12 was demonstrable. The toxin has no effect on the 45Ca accumulation coupled with the depolarization dependent release of catecholamines.

Adrenal Gland Neoplasms↗

Impaired circadian rhythmicity of beta-lipotrophin, beta-endorphin and ACTH in heroin addicts.

The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, beta-lipotrophin, (beta-LPH), beta-endorphin (beta-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (beta-LPH and beta-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a.m. the next morning. The means of the two 8 a.m. measurements of beta-LPH (2.67 +/- 0.34 fmol/ml, mean +/- SE), ACTH (2.74 +/- 0.71) and cortisol (218 +/- 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 +/- 0.61, 10.1 +/- 0.74 and 364 +/- 27, respectively, P less than 0.01) while beta-EP concentrations in heroin addicts (5.1 +/- 0.6) were similar to those of healthy volunteers (6.44 +/- 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol. In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗