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M Marta

Publications and source records attributed to M Marta.

At least 19 recordsLinked to original sources
PubMed2006

Activation measurement of the 3He(alpha,gamma)7Be cross section at low energy.

The nuclear physics input from the 3He(alpha,gamma)7Be cross section is a major uncertainty in the fluxes of 7Be and 8B neutrinos from the Sun predicted by solar models and in the 7Li abundance obtained in big-bang nucleosynthesis calculations. The present work reports on a new precision experiment using the activation technique at energies directly relevant to big-bang nucleosynthesis. Previously such low energies had been reached experimentally only by the prompt-gamma technique and with inferior precision. Using a windowless gas target, high beam intensity, and low background gamma-counting facilities, the 3He(alpha,gamma)7Be cross section has been determined at 127, 148, and 169 keV center-of-mass energy with a total uncertainty of 4%. The sources of systematic uncertainty are discussed in detail. The present data can be used in big-bang nucleosynthesis calculations and to constrain the extrapolation of the 3He(alpha,gamma)7Be astrophysical S factor to solar energies.

Journal Article↗
PubMed2005

Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

BACKGROUND: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. METHODS: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. RESULTS: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. CONCLUSION: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Adult↗
PubMed2000

Inhibition of AChE: structure-activity relationship among conformational transition of Trp84 and biomolecular rate constant.

In this study the authors attempt to correlate kinetic constants for carbamylation of AChE, by a series of carbamate inhibitors, with the conformational positioning of Trp84 in transition state complexes of the same carbamates with Torpedo AChE, as obtained by computerized molecular modelling. They present evidence for changes in the distance of the carbamates from the center of the indole ring which can be correlated with the bimolecular rate constants for inhibition. As a result the greater the distance from Trp84, the smaller the bimolecular inhibition constant value, ki (= k2/Ka), becomes. In conclusion, the value of the bimolecular rate constant for selected AChE inhibitors (structural changes that have been hypothesised or natural alkaloids of unknown activity) which possess similar size and rigidity, can be obtained. Under these conditions energy minimization alone seems to be sufficient even to accurately predict protein-substrate interactions that actually occur. Modelling studies also suggest that conformational re-orientation of Trp84 in the transition state could produce an overall movement of the Cys67-Cys94 loop.

Acetylcholinesterase↗
PubMed1999

Effects of the novel acetylcholinesterase inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine on locomotor activity and avoidance learning in mice.

The acetylcholinesterase reversible inhibitor N-octyl-1,2,3, 4-tetrahydro-9-aminoacridine (THA-C8) is a new synthesized derivative of tacrine (THA) characterized by an alkyl chain in the molecular structure which ameliorates the penetrability of the compound into the central nervous system. THA-C8 (0.1-5 mg/kg) significantly reduced spontaneous locomotor activity in CD1 mice at a dose of 3 mg/kg. Moreover, THA-C8 (0.2-2 mg/kg) significantly improved shuttle-box avoidance acquisition at doses (0.25, 0.3, 1 mg/kg) not affecting locomotion and that are much lower than the doses reported to be effective for THA in animal models. From the data reported it seems that the new compound could be interesting for therapeutic purposes.

Alzheimer Disease↗
PubMed1998

Anionic binding site and 2,3-DPG effect in bovine hemoglobin.

It is generally believed that bovine hemoglobin (BvHb) interacts weakly with 2,3-diphosphoglycerate (2,3-DPG) in a chloride-free media and not at all in the presence of physiological concentrations of chloride (100 mM). This lack of interaction has raised several questions at both structural and evolutionary levels. Results obtained in this study via 31P nuclear magnetic resonance (NMR) show that, even in the presence of 100 mM chloride ions, 2,3-DPG does, in fact, interact with bovine deoxy-Hb. This spectroscopic observation has been confirmed by oxygen binding experiments, which have also shown that, under certain conditions, chloride and 2,3-DPG may display a synergistic effect in modifying the oxygen affinity of bovine hemoglobin. It could be that this synergistic effect has its structural basis in a conformational modification induced by 2,3-DPG, possibly causing extra chloride anions to approach the positive charges which constitute the anion binding site. Another possibility, not necessarily an alternative, is the additional chloride binding site recently identified [Fronticelli, C., Sanna, M. T., Perez-Alvarado, G. C., Karavitis, M., Lu, A.-L., and Brinnigar, W. S. (1995) J. Biol. Chem 270, 30588-30592] involving lysine beta76 that in bovine Hb substitutes for the alanine residue present in human hemoglobin. All of these findings are in agreement with the very low enthalpy of oxygenation that characterizes bovine Hb when both chloride and 2,3-DPG are present in concomitance. The results reported here clearly show that bovine hemoglobin does react with 2, 3-DPG and is functionally affected by this organic phosphate. Hence, the very low intraerythrocytic concentration of 2,3-DPG (0.5 mM) in adult bovine red blood cells is the result of metabolic adaptation which cannot be explained solely by the different amino acid sequence at the level of the 2,3-DPG binding site.

2,3-Diphosphoglycerate↗
PubMed1998

The role of TRP84 in catalytic power and the specificity of AChE.

The structure-function relationship between the alkaloids physostigmine, physovenine and the three structurally related compounds were investigated by employing kinetic studies and molecular modeling. Crystallographic data from the X-ray conformation of the Torpedo californica acetylcholinesterase complex together with the transition state analog inhibitor m-(N,N,N,-Trimethylammonio) trifluoroacetophenone (TMTFA) was used as template onto which inhibitors were superimposed. Among the structural elements of the active site, TRP84 residue shows a versatile role. In fact, its aromatic electrons not only can be employed in pi-cation interactions, as is the case for ACh, but they can also provide a polarizable surface for van der Waals and London interactions.

Acetylcholinesterase↗
PubMed1997

Studies on a new series of THA analogues: effects of the aromatic residues that line the gorge of AChE.

A series of N-monoalkylsubstituted 1,2,3,4-tetrahydro-9-aminoacridines have been prepared after modelling simulation of the AChE-inhibitor complex. Molecular modelling has predicted a number of hydrophobic residues to be involved in the catalytic mechanism of this interaction between the binding sites of AChE and this series of aminoacridines. In these compounds the acridine moiety becomes sandwiched between the rings of PHE330 and TRP84. In particular, the alkyl chain shows the important role of aromatic groups as binding sites. Their in vitro inhibitory properties (enzyme from Electrophorus electricus) confirm the aromatic groups as a general and significant characteristic of the mechanism of AChE inhibition.

Acetylcholinesterase↗
PubMed1996

Bovine hemoglobin cross-linked through the beta chains: functional and structural aspects.

2-Nor-2-formylpyridoxal (NFPLP) has been synthesized and coupled to bovine Hb according to the procedure developed by Benesch and Benesch. The reaction of bovine Hb with NFPLP leads to a cross-linkage between the beta subunits, which greatly stabilizes the low affinity T state of the molecule and simultaneously abolishes the tendency of the tetramer to dissociate into alpha beta dimers. The functional properties, examined from both the equilibrium and kinetic points of view, indicate that the chemical modification affects the O2 affinity, abolishes cooperativity, and induces a slight decrease of the Bohr effect. From modeling studies we are confronted with two different structural alternatives; the cross-link of beta chains may be formed between lysine 82 of beta2 and the N terminus of methionine 2 of beta1 or between the two lysine 82 residues of both beta2 chains. Digestion of modified beta globin chains and isolation of the cross-linked peptide have showed that NFPLP cross-links Met-beta2 and Lys-beta82. This allowed discussion in some detail of the molecular basis of the Bohr effect of the modified bovine hemoglobin. On the whole, NFPLP-modified bovine Hb could be considered as a first step toward the synthesis of a potential blood substitute.

Animals↗
PubMed1993

"On the suggestion of Dr. Alzheimer I examined the following four cases." Dedicated to Gaetano Perusini.

Gaetano Perusini merits a great deal more credit for his work on the elaboration of the concepts regarding what is now called Alzheimer's disease (AD). Perusini's work in Alzheimer's laboratory and his subsequent studies have been, if not neglected, largely unmentioned. This article is an attempt to report a fascinating piece of medical history in order to redress the balance. Surely, Perusini's work deserves to be reexamined. The same applies to Fischer's investigation. Some of the puzzles discussed by Perusini are still unresolved.

Aged↗
PubMed1992

Physostigmine analogs anticholinesterases: effects of the lengthening of the N-carbamic chain on the inhibition kinetics.

Data are presented about the inhibitor power of new carbamates against acetylcholinesterase. The study was carried out on two series of physostigmine analogs, N-alkyl and N-methyl,N-alkylphysostigmines. For these inhibitors, the second-order rate constants for inhibition, ki, and the first-order rate constants of reactivation, k3, have been determined. From the reported results, electronic, hydrophobic and steric effects, due to the enhancement of the alkyl chain, may have influenced all kinetics parameters discussed. In comparison to physostigmine, both the new N-methyl,N-alkylphysostigmines and the N-alkylphysostigmines showed a non-linear decrease in the values of ki and k3. This study presents the hydrophobic interactions as an important factor not only in determining carbamylation but also decarbamylation rates constants.

Animals↗
PubMed1992

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History, Modern 1601-↗
PubMed1992

Synthesis of phenothiazine derivatives as potential inhibitors of phospholipase C.

In order to study the structure-activity relationships of phenothiazine derivatives inhibiting phosphatidylinositol-specific phospholipase C (PI-PLC), the synthesis of some phenothiazine amide, amine and ester derivatives was performed mainly by reacting 10H-phenothiazine-10-propanoyl chloride with some amines and alcohols; the resulting amides were reduced with borane to yield the corresponding amines. Starting from 2-chloro and 2-trifluoromethyl-10H-phenothiazine-10-propanoyl chloride two amides were synthesized. The inhibiting activity on PI-PLC from human platelets is reported.

Blood Platelets↗
PubMed1988

New analogs of physostigmine: alternative drugs for Alzheimer's disease?

The synthesis of a series of physostigmine analogs, in which the methylcarbamyl group has been substituted with monoalkylcarbamyl, dimethyl- and diethylcarbamyl groups, is reported. These compounds were prepared with the aim of investigating their possible therapeutic effects in the treatment of Alzheimer's type dementia. The new analogs of physostigmine are inhibitors of acetylcholinesterase from Electroforus electricus, with a value of the reactivation constant, k3 smaller than the one of physostigmine. The percentage of anticholinesterase activity in vitro and in vivo, the acute toxicity and some behavioural effects were also evaluated for selected derivatives. The reactivation constant, in vitro, supports the view that the derivatives described would be more suitable for therapeutic use than physostigmine.

Alzheimer Disease↗
PubMed1988

Inhibition of acetylcholinesterase by new physostigmine derivatives.

The kinetics of inhibition of acetylcholinesterase (AChE, EC 3.1.1.7) from electric eel by new physostigmine derivatives in which the methylcarbamic group has been substituted with monoalkylcarbamic, dialkylcarbamic and phenylcarbamic groups was studied. The new compounds are competitive inhibitors of AChE and show a lower anticholinesterase activity than physostigmine. The anticholinesterase activity, the bimolecular rate constant ki and the carbamylation constant k2 have been measured for some selected derivatives.

Animals↗
PubMed1987

A long-lasting cholinesterase inhibitor affecting neural and behavioral processes.

A series of analogues of physostigmine were prepared with the aim of investigating their inhibitory effects on acetylcholinesterase in the treatment of Alzheimer's disease. One of the isomers prepared was evaluated for its anticholinesterase activity in vivo, acute toxicity, and some behavioral effects. This compound was a competitive inhibitor of the enzyme and was found to antagonize the stimulating effect produced by scopolamine on locomotor activity and to facilitate memory consolidation.

Acetylcholinesterase↗