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Biomedical subjects

A Trovato

Publications and source records attributed to A Trovato.

At least 19 recordsLinked to original sources

Design of amino acid sequences to fold into C(alpha)-model proteins.

In order to extend the results obtained with minimal lattice models to more realistic systems, we study a model where proteins are described as a chain of 20 kinds of structureless amino acids moving in a continuum space and interacting through a contact potential controlled by a 20x20 quenched random matrix. The goal of the present work is to design and characterize amino acid sequences folding to the SH3 conformation, a 60-residue recognition domain common to many regulatory proteins. We show that a number of sequences can fold, starting from a random conformation, to within a distance root-mean-square deviation between 2.6 and 4.0 A from the native state. Good folders are those sequences displaying in the native conformation an energy lower than a sequence-independent threshold energy.

Amino Acid Sequence↗

Anti-inflammatory activity of extract and fractions from Nepeta sibthorpii Bentham.

Several species of Nepeta genus are utilized in folk medicine for treatment of contusions, rheumatic pains, fever, cutaneous eruptions. Some species are employed for their anti-inflammatory properties. In this paper, we report the results of phytochemical studies on aerial parts of Nepeta sibthorpii Bentham (Lamiaceae), an endemic plant of Greece. The bioassay-guided fractionation of methanol extract led to the isolation of ursolic acid and polyphenol fraction. By HPLC, we determined some phenolics: chlorogenic acid (0.315 mg/g) and the flavonoids rutin (0.091 mg/g), luteolin-7-O-glucoside (0.387 mg/g) and a luteolin derivative. We assayed the radical scavenging activity of Nepeta sibthorpii methanol extract by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Moreover, we studied the anti-inflammatory activity of Nepeta sibthorpii methanol extract (50 mg/kg, os), ursolic acid and polyphenol fraction (dose corresponding to 50 mg/kg of methanol extract, os) in the carrageenan-induced paw oedema in rat. In this experimental model, we observed a significant inhibition of paw oedema. We suppose that the anti-inflammatory effect of methanol extract could be related to the free radical scavenging activity and that it depends on a synergic action of all the components of the methanol extract, even if ursolic acid can be considered the main responsible for this activity.

Animals↗

Chiral 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] with anti-inflammatory activity. Part 11: evaluation of COX-2 selectivity and modelling.

Anti-inflammatory/analgesic 3,3'-(1,2-ethanediyl)-bis[2-(3,4-dimethoxyphenyl)-4-thiazolidinones] 1, obtained as racemic mixtures (a) and mesoforms (b), have two equivalent stereogenic centres (C-2 and C-2') and exist as RR, SS and RS isomers. The enantioseparation of 1a provided the single enantiomers that displayed different in vitro cyclooxygenase-1/cyclooxygenase-2 selectivity ratios. In particular the dextrorotatory compound is a highly selective COX-2 inhibitor and the levorotatory one is moderately selective. Instead, RS-meso isomer (1b) exhibited similar levels of inhibitory activity on both COX isozymes. The diastereo- and enantioselectivity has been explained by molecular modelling of RR, SS and RS compounds into COX-1 and COX-2 binding sites. Theoretical results indicated SS>RS>RR affinity order towards COX-2 isoenzyme, in agreement with in vitro and previous in vivo pharmacological results.

Anti-Inflammatory Agents, Non-Steroidal↗

Anticonvulsant and sedative effects of Salvadora persica L. stem extracts.

The effect of Salvadora persica L. stem extracts on the potentiation of sodium pentobarbital activity and on generalized tonic-clonic seizure produced by pentylenetetrazol (PTZ) on the rat is reported. The extracts of Salvadora persica L. extended sleeping-time and decreased induction-time induced by sodium pentobarbital; in addition it showed protection against pentylenetetrazol-induced convulsion by increasing the latency period and diminishing the death rate.

Animals↗

Biological effect of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter. Note I: diuretic activity.

In this work we studied in rat the diuretic activity of Opuntia ficus indica (L.) Mill. (Cactaceae) waste matter. The cladodes, flowers and non commerciable fruits were collected in S. Cono (CT, Sicily) cultivation. Acute and chronic diuretic activity of 15% infusion of cladodes, flowers and fruits were assayed. Natriuresis, kaliuresis and the activity on fructose-induced hyperuricemia was also studied. The results show that O. ficus indica cladode, fruit and flower infusions significantly increase diuresis. This effect is more marked with the fruit infusion and it is particularly significant during the chronic treatment. The fruit infusion shows also antiuric effect. In all experiments cladode, flower and fruit infusions showed a modest but not significant increase in natriuresis and kaliuresis.

Administration, Oral↗

Synthesis and antiinflammatory, analgesic activity of 3,3'-(1,2-ethanediyl)-bis[2-aryl-4-thiazolidinone] chiral compounds. Part 10.

In this note, the synthesis and structure-activity relationships of a new series of 2R,2'R/2S,2'S and 2R,2'S-meso 3,3'-(1,2-ethanediyl)-bis[2-aryl-4-thiazolidinones] are described. Antiinflammatory activity was investigated by the carrageenin-induced paw edema test and analgesic activity by acetic acid writhing and hot plate tests in rats. All compounds displayed ulcerogenic effects and acute toxicity much lower than indomethacin and phenylbutazone. Meso isomers (b) showed better pharmacological profiles than corresponding racemates (a). Methoxy substitution patterns of the aryls on stereogenic carbons are generally the most favorable on the pharmacological profile.

Analgesics, Non-Narcotic↗

Phase diagram of force-induced DNA unzipping in exactly solvable models.

The mechanical separation of a double helical DNA structure induced by forces pulling apart the two DNA strands ("unzipping") has been the subject of recent experiments. Analytical results are obtained within various models of interacting pairs of directed walks in the (1,1,ellipsis,1) direction on the hypercubic lattice, and the phase diagram in the force-temperature plane is studied for a variety of cases. The scaling behavior is determined at both the unzipping and melting transitions. We confirm the existence of a cold denaturation transition recently observed in numerical simulations: for a finite range of forces, the system is unzipped by decreasing the temperature. The existence of this transition is rigorously established for generic lattice and continuum space models.

Base Pairing↗

Optimal shapes of compact strings.

Optimal geometrical arrangements, such as the stacking of atoms, are of relevance in diverse disciplines. A classic problem is the determination of the optimal arrangement of spheres in three dimensions in order to achieve the highest packing fraction; only recently has it been proved that the answer for infinite systems is a face-centred-cubic lattice. This simply stated problem has had a profound impact in many areas, ranging from the crystallization and melting of atomic systems, to optimal packing of objects and the sub-division of space. Here we study an analogous problem--that of determining the optimal shapes of closely packed compact strings. This problem is a mathematical idealization of situations commonly encountered in biology, chemistry and physics, involving the optimal structure of folded polymeric chains. We find that, in cases where boundary effects are not dominant, helices with a particular pitch-radius ratio are selected. Interestingly, the same geometry is observed in helices in naturally occurring proteins.

Collagen↗

Central motor conduction to lower limb after transcranial magnetic stimulation in spinocerebellar ataxia type 2 (SCA2).

OBJECTIVES: To evaluate central motor conduction to lower limbs in spinocerebellar ataxia type 2 (SCA2). METHODS: Transcranial magnetic stimulation was performed to study the corticospinal tracts of 18 patients with SCA2. RESULTS: Central motor conduction time (CMCT) to lower limbs and thresholds were abnormal in 8 patients (44%); CMCT and thresholds were significantly correlated with disease duration and disability. CONCLUSIONS: Corticospinal tract involvement is more frequent than previously reported in SCA2. Prolonged CMCT and increased threshold should not be used to differentiate between various type of autosomal dominant cerebellar ataxia. Similar to that reported in Friedreich's ataxia, we suggest that examining central motor conduction to the lower limbs may assist in evaluating the progressive steps of neurodegeneration in SCA2.

Adult↗

Identification of SCA2 mutation in cases of spinocerebellar ataxia with no family history in mid-eastern Sicily.

Differential diagnosis between autosomal dominant cerebellar ataxia type I (ADCA I) and idiopathic cerebellar ataxia type P (IDCA-P) is very difficult given only clinical and neuroradiological data. The only certain distinctive characteristic is the presence or absence of family history. We observed 7 patients with late-onset cerebellar ataxia associated with other non-cerebellar signs and without a family history of the disease in which clinical signs were comparable to symptoms found in SCA2. The neuroradiological study showed olivopontocerebellar atrophy in all patients and the presence of hyperintensity of the transverse pontine fibers in 6 patients (85. 6%); molecular analysis showed SCA2 mutations in 2 patients. We also report the case of a patient who was initially considered as IDCA-P but who was later correctly identified as SCA2 with an atypical family history (false IDCA-P), after a genetic mutation was found and following an interview with the mother. Our data suggest that spinocerebellar ataxia syndrome should be defined as idiopathic not only after having excluded the possible symptomatic causes but also in the absence of family history, after having excluded the presence of genetic mutation. We believe that family history, in late-onset spinocerebellar ataxia, cannot be considered as the differential criterion among hereditary (ADCA-I) and non-hereditary (IDCA-P) forms; molecular analysis is required for a correct diagnosis.

Adult↗

Salvadora persica L.: hypolipidemic activity on experimental hypercholesterolemia in rat.

Stems of Salvadora persica are widely used as tooth cleaning sticks in Arabic countries and decoctions show hypocholesterolemic properties. The effects of prolonged administration of a lyophilized stem decoction of Salvadora persica were evaluated in diet-induced rat hypercholesterolemia. The preparation was administered for 15 and 30 days (by gavage at a dose of 500 mg/kg in an aqueous vehicle in a volume of 0.5 ml/100 g b.w.). Cholesterol, HDL, LDL and triglyceride plasma levels were assayed. The results showed that the S. persica decoction significantly lowered cholesterol and LDL plasma levels in rats, proving to be more active at 30 days of treatment. The systemic administration of Triton results in a rise in plasma cholesterol and triglyceride levels. The results obtained show that S. persica decoction was inactive at 18 hr after treatment, whereas at 27 hr, it was able to reduce cholesterol and LDL plasma levels. In all experiments HDL and triglycerides were unchanged.

Africa↗

3,3'-Bi(1,3-thiazolidin-4-one) system. VIII. 3,3'-(1,2-Ethanediyl) derivatives and corresponding 1,1'-disulfones: synthesis, stereochemistry and antiinflammatory activity.

To deeply investigate the influence of lipophilicity, phenyl substitution patterns and stereo-chemistry on pharmacological profiles of chiral bisarylthiazolidinones, frequently endowed with stereoselective antiinflammatory, analgesic, antihistaminic activities, we synthesized and explored some 3,3'-(1,2-ethanediyl) analogues 1-4, along with their S-oxidized derivatives 5-8. Each derivative can be isolated as 2R, 2'R/2S, 2'S (a) and 2R, 2'S- or 2S, 2'R- meso (b) diastereomers, which were explored by means of carrageenin edema test, acetic acid writhing and hot plate tests, and also tested for gastrolesive potential and LD50. Independently of lipophilic and electronic features, disulfides 3b, 4b and disulfones 7a, 8a, 8b displayed interesting activity levels which appear to be mainly linked to the disubstitution pattern on benzenic rings.

Animals↗

In vitro cytotoxic effect of some medicinal plants containing flavonoids.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck), Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa canina L. and Ruta graveolens L. have been studied. The cytotoxicity of the drugs assayed was evaluated "in vitro" by means of the dye test using cells of the Yoshida ascites sarcoma. The aqueous extract of Citrus sinensis L. (Osbeck); the petroleum ether extract of Glycyrrhiza glabra L.; the ethanolic and petroleum ether extracts of Rosa canina L. and the petroleum ether extract of Ruta graveolens L. showed a quite significative cytotoxic effect.

Animals↗

Aminopyrazinyl derivatives: synthesis and evaluation of antiinflammatory and related activities.

Some amides, 1-substituted methylenediamines and 2-substituted thiazolidin-4-ones, all containing the aminopyrazinyl moiety, were synthesized and tested in the experimental models of acute and chronic inflammations and as potential analgesic agents. The first series of compounds are inactive, whereas the N,N'-di-(2-pyrazinyl)-methylene-diamines and the 3-(2'-pyrazinyl)-thiazolidinones 6, 7, 11, 12 and even more 16 and 17 were found to be endowed with antiinflammatory and analgesic properties and low acute toxicity, the two latter being the most interesting.

Animals↗