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S Giuffrida

Publications and source records attributed to S Giuffrida.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical and molecular analysis of 11 Sicilian SCA2 families: influence of gender on age at onset.

Autosomal dominant cerebellar ataxias (ADCAs) are a complex group of slowly progressive neurodegenerative disorders characterized by gait and stance ataxia, dysarthria and other symptoms of nervous system involvement. ADCA type I is the commonest form and is genetically heterogeneous; several loci have been identified. Spinocerebellar ataxia type 2 (SCA2) has been mapped to chromosome 12, with expanded cytosine-adenine-guanine (CAG) repeats being identified as the mutational cause of the disease. We investigated 15 families, all originating from mid-eastern Sicily, with ADCA type I; molecular studies performed in 12 families showed the SCA2 mutation to be present in 11 of them (91.6%) - the highest occurrence so far reported in the literature. The CAG repeat of the affected alleles varied between 34 and 44 repeats. Age at onset and repeat length revealed an inverse correlation. Mean age at onset was 37.32 +/- 16. 74 years, and occurred earlier in males than in females. There were no differences in mean CAG repeat units between the sexes. However, a higher instability of CAG repeats was observed for paternal transmission than for maternal transmission. Age at onset and anticipation were not related to parental transmission. Our data suggest that in SCA2 an unknown sex-linked factor may play a role in the modulation of toxic effects of the polyglutamine tract.

Adolescent↗
PubMed1999

Molecular mechanisms of photosensitization induced by drugs. XII. Photochemistry and photosensitization of rufloxacin: an unusual photodegradation path for the antibacterials containing a fluoroquinolone-like chromophore.

The UVA irradiation of 9-fluoro-2,3-dihydro-10-4'-methyl-1' -piperazinyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzo-thiazine-6-carboxylic acid, rufloxacin, a fluoroquinolone antibacterial that shows photosensitizing properties toward biological substrates, leads to formation of two main steady photoproducts characterized by a decarboxylation process and an opening of the piperazinyl ring, respectively. The deprotonation of the 10-piperazinyl group and the dissociation of the 6-carboxyl group of rufloxacin are strictly pH dependent. The photosensitizing activity was tested toward membranes as biological targets. Red blood cell hemolysis and lipid peroxidation were considered as markers of photosensitization. Ultraviolet A-induced damage is strongly influenced by the presence of oxygen, it is triggered by transient species, such as singlet oxygen and free radicals, photogenerated via rufloxacin irradiation, whereas no drug photoproduct is involved in the photosensitization process.

Anti-Infective Agents↗
PubMed1998

Swellable microparticles containing Suprofen: evaluation of in vitro release and photochemical behaviour.

Suprofen, an anti-inflammatory drug was incorporated in polymer networks based on biocompatible macromolecules, such as alpha,beta-polyasparthydrazide (PAHy) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) crosslinked by glutaraldehyde or gamma-rays, respectively. Swelling tests carried out in aqueous media showed that pH value affects the swelling degree of the prepared hydrogels. In vitro release tests were performed in simulated gastrointestinal fluids (pH 1/6.8) using the pH variation method and in phosphate-buffered saline, pH 7.4. Experimental data indicated that Suprofen was released in a sustained way both from PAHy and PHEA microparticles. Further, incorporation of Suprofen in PAHy and PHEA networks provided a significant reduction of the drug photosensitizing activity, as evidenced by in vitro hemolysis tests.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Rapid touchdown PCR assay for the molecular diagnosis of spinocerebellar ataxia type 2.

Seven different chromosomal loci, designated SCA1 to SCA7 (spinocerebellar ataxias), have been identified as responsible for autosomal dominant cerebellar ataxias. Five genes (SCA1, 2, 3, 6, 7) have been cloned to date and show a single type of mutation, an unstable expansion of a CAG repeat coding for a polyglutamine stretch in the corresponding protein. We describe an improved polymerase chain reaction assay, based on a touchdown protocol, for the diagnosis of spinocerebellar ataxia type 2. This method produces an efficient amplification of both normal and pathological alleles and no radioactive labelling is necessary to observe the amplification products. The pathological alleles are identified by a simple non-denaturing polyacrylamide electrophoretic separation followed by ethidium bromide staining. A comparison of this technique with previously reported methods confirmed its utility for the rapid molecular diagnosis of spinocerebellar ataxia type 2. We found that the spinocerebellar ataxia type 2 mutation is responsible for 88% of the examined autosomal dominant cerebellar ataxia type 1 families in our territory (eastern Sicily). With the rapid touchdown polymerase chain reaction method, the trinucleotide expansion was also observed in 2 ataxic patients without family history of the disease, suggesting the necessity for analysis of spinocerebellar ataxia type 2 expansion even in sporadic patients.

Alleles↗
PubMed1998

Reversible palsy of the hypoglossal nerve complicating infectious mononucleosis in a young child.

We report a 7-year-old boy with serologic evidence of active Epstein-Barr virus (EBV) infection who developed transient unilateral hypoglossal nerve palsy, with complete recovery within 21 days. This is, to our knowledge, the youngest reported patient with isolated hypoglossal nerve palsy in the context of EBV infection. Acute EBV infection should be considered early in the evaluation of children with twelfth nerve palsy in order to avoid extensive ancillary testing.

Child↗
PubMed1998

Sodium fusidate in Gillain-Barré syndrome: a case report.

A patient with Guillain-Barré syndrome is reported on who responded favourably to a short course treatment with the novel immunosuppressant sodium fusidate (Fucidin), given at a daily dose of 1.5 g for one week. Along with prompt and clear cut clinical improvement, treatment with Fucidin was associated with a rapid decline in the blood concentrations of inflammatory cytokines presumably implicated in the pathogenesis of Guillain-Barré syndrome such as interleukin-2, interferon-gamma, and tumor necrosis factor-alpha. The ex vivo production of these cytokines was also markedly diminished compared with pretreatment values. Fucidin was well tolerated and no clinical or biochemical side effects were seen.

Dose-Response Relationship, Drug↗
PubMed1998

pH effects on the spectroscopic and photochemical behavior of enoxacin: a steady-state and time-resolved study.

The spectroscopic and photochemical behavior of Enoxacin (ENX), 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 1,8-naphthyridine-3-carboxylic acid, has been investigated in aqueous solutions between pH 3.5 and pH 12. The absorption and emission properties of ENX are strongly affected by pH. The fluorescence quantum yield, 4 x 10(-3) at pH 3.5, increases by a factor of two on going to neutral pH while a strong reduction is observed at alkaline pH. The photodegradation quantum yield also depends on pH, being maximum in neutral conditions (ca 0.04). Nanosecond flash photolysis experiments confirm that the yield of absorbing transients is maximum at neutral pH while it decreases to zero at acid and alkaline pH. These results indicate that both the dissociation of the carboxylic group and the protonation of the piperazinyl residues are key steps for the formation of the photochemically active form of ENX. Loss of F by heterolytic cleavage of the C-F bond is proposed to occur from the triplet state of the zwitterion with formation of a carbocation. A path for the evolution of this intermediate to the final product is also proposed.

Anti-Infective Agents↗
PubMed1998

Molecular mechanism of photosensitization. XI. Membrane damage and DNA cleavage photoinduced by enoxacin.

The photosensitizing activity of enoxacin, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 1,8-naphthyridine-3-carboxilic acid (ENX), toward membranes and DNA has been studied, taking into account human erythrocyte photohemolysis, unilamellar liposome alterations and plasmid pBR322 DNA photocleavage. Hydroxyl radicals and an aromatic carbene generated from ENX photodefluorination seem to be the active intermediates involved in the photosensitization process. The steady-state photolysis products do not participate in the process. The mechanism of photosensitization responsible for the membrane damage depends on the oxygen concentration and follows a different path with respect to that operative for DNA cleavage. Between oxygenated radicals, the hydroxyl seems the species mainly responsible for membrane damage, whereas DNA cleavage is mainly produced by the carbene intermediate. A molecular mechanism of the photosensitization induced by ENX is proposed.

DNA↗
PubMed1997

Cervical epidural abscess: serial MRI study.

Cervical epidural abscess (CEA) at first often goes unrecognized and it is to be suspected in patients suffering by spinal ache, root pain, neurological deficit and fever. Staphylococcus aureus is the most frequent etiologic agent. At present MRI is the study of choice for the diagnosis of CEA. We suggest a serial MRI study in close time in at first doubtful cases of CEA. When the responsible organism is not identified and there are also compressive signs of the spinal cord, the treatment of choice is surgical decompression followed by selective antibiotic therapy. The duration of antibiotic therapy may be established not only by clinical judgement, but also by serial MRI study, which gives direct information about disease evolution.

Abscess↗
PubMed1996

Molecular mechanism of drug photosensitization: VIII. Effect of inorganic ions on membrane damage photosensitized by naproxen.

The inhibitory effect of Cu2+, Mn2+, Co2+, and I- on naproxen-induced photohemolysis was investigated. In order to better understand this effect, these ions were also tested for lipid peroxidation and protein crosslinking, which are among the main processes involved in erythrocyte membrane damage. The overall results support the hypothesis that metal cations act via a redox scavenging of the radicals which are produced on the lipid component of the membrane. This process occurs through hydrogen abstraction operated by photogenerated naproxen radicals. Moreover, copper can also act as a superoxide anion scavenger: its decay is noxious in photohemolysis, whereas it is not in lipid peroxidation. Metal cations, besides, are not able to scavenge protein crosslinking. On the other hand, iodide is able to reduce both processes because it acts as a heavy atom, favoring intersystem crossing to the unreactive triplet state of the drug, thus reducing naproxen photolysis and, as a consequence, the amount of the damaging species produced. This mechanism was supported by luminescence experiments performed in the absence and in the presence of iodide.

Cations, Divalent↗
PubMed1996

Efficacy of mipragoside ophthalmic gel in vernal keratoconjunctivitis.

To evaluate the efficacy of Mipragoside, a ganglioside derivative, in vernal keratoconjunctivitis we performed a controlled randomised clinical trial involving 24 patients (mean age 10 +/- 3.4 years, range 5-20 years). Patients received either Mipragoside 0.5% aqueous ophthalmic gel or placebo four times a day for 2 weeks after a week of treatment with placebo. Ocular signs and symptoms were evaluated and considered for statistical analysis. Results show that Mipragoside significantly reduces all symptoms, being most effective on itching (p = 0.01; p = 0.0001) and hyperaemia (p = 0.01; p = 0.0006) after 1 and 2 weeks respectively when compared with placebo. Physician judgement of drug efficacy at the end of treatment was significantly in favour of Mipragoside (p = 0.0001) compared with placebo. We conclude that Mipragoside topical treatment improves symptoms of patients with vernal keratoconjunctivitis and we postulate a possible anti-inflammatory activity of this compound.

Administration, Topical↗
PubMed1996

Molecular mechanism of drug photosensitization. IX. Effect of inorganic ions on DNA cleavage photosensitized by naproxen.

Photocleavage of DNA induced by naproxen and the correlated protective effect by some inorganic ions have been considered. The presence of a DNA complex is suggested and only associated naproxen seems to be responsible for the cleavage, for which the quantum yield of single strand breaks was calculated. The inorganic ions I-, Mn2+, Co2+ and Cu2+ decrease naproxen-photoinduced DNA cleavage. Iodide acts by a heavy atom mechanism, thus inhibiting naproxen photolysis and decreasing the amount of free radicals responsible for the photocleavage both in aerobic and anaerobic conditions. Metallic ions protect only within a range of concentrations, as for higher amounts damaging processes are observed. The protective efficiency of cations decreases with the increase of free drug concentration in the bulk of the solution, due to their involvement in the scavenging of naproxen radicals generated by photolysis of the free drug. In the presence of EDTA the cations show a better protective action. The most likely hypothesis is an inhibiting effect on the damaging processes via a redox cycle. The different behaviors of copper and of the two other cations can be justified by the influence of redox potentials of free and complexed metals and by the superoxide dismutase-like activity of copper.

Animals↗
PubMed1995

Antioxidant effect of copper(II) on photosensitized lipid peroxidation.

Unilamellar liposomes (LH) of phosphatidylcholine (PC), dispersed in phosphate buffer at pH 7 (PB), underwent lipid peroxidation and lysis with release of entrapped glucose-6-phosphate when irradiated with UVA light in the presence of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KPF) or 2-(6-methoxy-2-naphthyl)propionic acid (naproxen, NAP), which were used as photosensitizers. Lipid photoperoxidation and consequent lysis were reduced when copper(II), up to 5 microM, was present in the irradiated samples. Suitable experiments were performed to evidence the species responsible for the lipid peroxidation, the copper effect on the drug photodegradation, and the mechanism of the copper antioxidant activity. The overall results suggest that the photoperoxidation was probably initiated by organic radicals obtained from the irradiation of KPF and NAP and the inhibition by copper could be attributed to its interaction with the peroxyl radicals of the drug and/or the liposomes, breaking the propagation of the radical chain.

Amino Acid Sequence↗
PubMed1995

Antioxidant effect of inorganic ions on UVC and UVB induced lipid peroxidation.

Phosphate buffer suspensions of unilamellar liposomes of phosphatidylcholine were irradiated with UVC (254 nm) and UVB (300 nm) light. The irradiation provoked lipid peroxidation and liposome lysis with release of entrapped glucose-6-phosphate. At the same intensity of absorbed light, the photochemical effect at 254 nm is higher than at 300 nm. The addition of copper(II) and manganese(II) reduced both the peroxidation and the lysis. The copper showed an inhibitory effect only on the process provoked by the 254 nm irradiation, whereas the manganese was efficient both at 254 and 300 nm. The results are interpreted with a mechanism of peroxidation and quenching, involving photoformation of peroxyl radicals that are scavenged by manganese(II) and copper(I), with consequent breaking of the radical chain and reduction of the peroxidation rate. The copper(I), which is the active species, can be formed only at 254 nm by electron capture. The experimental data fit the kinetic equations obtained by the proposed mechanism by means of computer software.

Antioxidants↗
PubMed1995

Molecular mechanism of drug photosensitization. Part 6. Photohaemolysis sensitized by tolmetin.

The photosensitizing properties of tolmetin, 5-(p-toluoyl)-1-methyl-2-pyrrolyacetic acid (TLM), have been studied in vitro following the lysis of erythrocytes in phosphate buffer suspensions irradiated with UVA light in the presence of the drug. It was found that the phototoxic properties of the drug are negligible in nitrogen and significant in aerated medium, but that they decrease in oxygen-saturated solution. The investigation of the drug photolysis showed that TLM undergoes photodecarboxylation to p-tolyl 1,2-dimethyl-5-pyrrolyl ketone in nitrogen and to p-tolyl 1-methyl-2-hydroxymethyl-5-pyrrolyl ketone and 5-(p-toluoyl)-1-methyl-2-pyrrole carbaldehyde in air. These photoproducts also undergo photodegradation. The comparison between the photohaemolysis and photolysis results and the effect of suitable additives such as sodium azide, mannitol, butylated hydroxy-anisole, reduced glutathione, superoxide dismutase and copper (II) suggest that the phototoxicity of TLM can be attributed essentially to singlet oxygen in the first step and to its photoproducts when they accumulate and compete with the starting drug in light absorption. Their phototoxic effect is much higher with respect to that of TLM, as shown by comparison of the doses needed to attain 50% photohaemolysis.

Aerobiosis↗
PubMed1995

Molecular mechanism of drug photosensitization. 7. Photocleavage of DNA sensitized by suprofen.

Ultraviolet-A irradiation of a suprofen (2-[4-2(2-thenoyl) phenyl]propionic acid) (SPF) buffered solution (pH 7.4) in the presence of supercoiled pBR322 DNA leads to single strand breaks with the formation of an open circular form and subsequent linearization of the plasmid. On the basis of agarose gel electrophoresis data of samples irradiated in an air-saturated solution or in an oxygen-modified atmosphere, and the effects of sodium azide, D20, mannitol, copper(II), superoxide dismutase, 2-H-propanol, deferoxamine and surfactants, we suggest a photosensitization mechanism involving singlet oxygen and free radicals. The higher rate of photocleavage in nitrogen compared to that in an air-saturated solution and the results obtained from oxygen consumption measurements support the hypothesis that both the type I and type II photosensitization mechanisms are operative and that oxygen quenches the excited state of the irradiated drug. The photosensitization model applied was in agreement with that previously applied to cell membrane SPF photoinduced damage. Interaction of the drug with DNA, studied through circular dichroism and fluorescence anisotropy, probably occurs through a surface binding mode. The experimental techniques used for assessing the photodamaging activity of this drug may be useful for screening of phototoxic compounds in the environment and for determining the active species involved.

Binding Sites↗
PubMed1994

Inhibition of photohemolysis by copper(II) complexes with SOD-like activity.

Red blood cell lysis photosensitized by Ketoprofen, 2-(3-benzoxyphenyl)propionic acid (KPF), was investigated in the presence of some copper(II) complexes with linear and cyclic dipeptides as well as functionalized beta-cyclodextrins with SOD-like activity with the aim of ascertaining their protective activity towards the photoinduced cell damage. The comparison between the decrease of photolytic activity caused by these complexes and their superoxide dismutase activity showed an appreciable correlation. The correct determination of species existing in experimental conditions was obtained through a simulation approach based on the knowledge of the stability constants of the complexes.

Amino Acid Sequence↗