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Biomedical subjects

S Giuffrida

Publications and source records attributed to S Giuffrida.

At least 19 recordsLinked to original sources

Molecular dynamics simulation of sucrose- and trehalose-coated carboxy-myoglobin.

We performed a room temperature molecular dynamics (MD) simulation on a system containing 1 carboxy-myoglobin (MbCO) molecule in a sucrose-water matrix of identical composition (89% [sucrose/(sucrose + water)] w/w) as for a previous trehalose-water-MbCO simulation (Cottone et al., Biophys J 2001;80:931-938). Results show that, as for trehalose, the amplitude of protein atomic mean-square fluctuations, on the nanosecond timescale, is reduced with respect to aqueous solutions also in sucrose. A detailed comparison as a function of residue number evidences mobility differences along the protein backbone, which can be related to a different efficacy in bioprotection. Different heme pocket structures are observed in the 2 systems. The joint distribution of the magnitude of the electric field at the CO oxygen atom and of the angle between the field and the CO unit vector shows a secondary maximum in sucrose, absent in trehalose. This can explain the CO stretching band profile (A substates distribution) differences evidenced by infrared spectroscopy in sucrose- and trehalose-coated MbCO (Giuffrida et al., J Phys Chem B 2004;108:15415-15421), and in particular the appearance of a further substate in sucrose. Analysis of hydrogen bonds at the protein-solvent interface shows that the fraction of water molecules shared between the protein and the sugar is lower in sucrose than in trehalose, in spite of a larger number of water molecules bound to the protein in the former system, thus indicating a lower protein-matrix coupling, as recently observed by Fourier transform infrared (FTIR) experiments (Giuffrida et al., J Phys Chem B 2004;108:15415-15421).

Binding Sites↗

Prevalence of Parkinson's disease: a door-to-door survey in rural Bolivia.

A door-to-door survey was carried out in rural areas of the Cordillera Province, Bolivia, to determine the prevalence of Parkinson's diseases (PD) in a sample of 9955 subjects. We found five cases of PD on prevalence day, November 1, 1994. The crude prevalence was 50.2/100,000 (95% CI 18.5-124.5) and 286/100,000 (95% CI 28-543) in subjects aged 40 years or more. Our prevalence is close to rates found in other in developing countries.

Adult↗

Improvement of diabetic autonomic gustatory sweating by botulinum toxin type A.

Fourteen diabetic subjects with gustatory sweating were treated by intracutaneous injections of botulinum toxin type A into the affected facial skin areas. In all subjects, sweating (measured by Minor starch iodine test) ceased within 4 days, with the maximal follow-up time lasting 24 weeks. This therapeutic approach, which could be used to reduce the severity of diabetic gustatory sweating, appears to be long lasting, adverse effect free, and minimally invasive.

Aged↗

Mutism after surgical removal of a cerebellar tumor: two case reports.

The authors report two pediatric cases of transient mutism that occurred after surgical removal of a medulloblastoma and a pilocytic astrocytoma of the vermis and discuss the pathophysiology of this syndrome. Transient mutism has been described for the first time quite recently, even in cases where these tumors were also surgically removed before. Perhaps improvement in imaging and in surgical techniques made neurosurgeons more daring and some interventions that were judged impossible are routinely performed today. If this is the case, postoperative transient cerebellar mutism might be considered the price that must be paid in order to cure more patients with cerebellar tumors.

Astrocytoma↗

The photochemistry of flutamide and its inclusion complex with beta-cyclodextrin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways.

The photochemistry of the anticancer drug flutamide (FM), 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide, in homogeneous media and in the beta-cyclodextrin (beta-CD) cavity has been investigated. The photoreactivity of the free molecule has been rationalized on the basis of an intramolecular nitro to nitrite rearrangement followed by cleavage of the nitrite intermediate. The twisted geometry of the nitro group with respect to the aromatic plane plays a key role in triggering such a photoprocess. Incorporation of FM in the beta-CD cavity leads to dramatic effects on both the efficiency and the nature of the photochemical deactivation pathways of the guest molecule. A 20-fold increase in the FM photodecomposition quantum yield and the formation of photoproducts originated by both reduction of the nitro group and cleavage of the amide bond were observed in the presence of the macrocycle. Such a behavior cannot be attributed exclusively to the micropolarity of beta-CD and/or to its role as a reactant. The induced circular dichroism spectra and the nature of the photoproducts formed in these experimental conditions provide indications that the photoreactivity in the beta-CD microenvironment could likely be mediated by structural changes of FM upon complexation.

Antineoplastic Agents, Hormonal↗

Diabetes insipidus in neurobrucellosis.

Brucellosis is an infection due to Brucella species and is characterized by acute febrile illness, chilly sensations, sweats, weakness, generalized malaise, body aches and headache. The involvement of the nervous system is rare. A few cases have been reported with symptoms and sign of optic neuritis, meningoencephalitis, meningomyelitis and cranial nerve palsy. We report a case with culture proven neurobrucellosis who presented with diabetes insipidus along with systemic signs. Neuroimaging revealed multiple lesions in brain parenchyma, including the suprasellar region. Both diabetes and suprasellar lesions improved markedly with specific antibiotic therapy.

Brain↗

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↗

Improvement of the ocular surface using hypotonic 0.4% hyaluronic acid drops in keratoconjunctivitis sicca.

BACKGROUND: The ocular surface changes of keratoconjunctivitis sicca (KCS) could be the result of the effect of an altered tear film on the epithelial environment. PURPOSE: To evaluate the possibility of improving the environmental conditions of the ocular surface by lowering tear osmolarity, increasing tear film volume and stabilising the tear film. Also, to study the effect of such an improvement on the epithelial cells of the ocular surface. METHODS: One hundred and thirty-five patients with a diagnosis of KCS were treated on a randomised basis with either unpreserved hypotonic 0.4% hyaluronic acid (HHA) eye drops or 0.3% hydroxypropylmethylcellulose plus 0.1% Dextran 70 (HPMC) eye drops 6 times a day for 60 or 90 days. In all patients a Schirmer I test, break-up time (BUT), ocular surface staining with 1% Bengal Rose, or 2% fluorescein, as well as subjective symptoms, were recorded before and 15, 30 and 60 days after the beginning of the study. Patients were divided into three subgroups and the effect of the treatment was studied using three different techniques: the tear ferning test, conjunctival impression cytology and tear osmolarity measurement. RESULTS: Improvements in BUT, vital staining, Schirmer I and symptoms were recorded in both groups of treatment, with significant differences for patients treated with 0.4% HHA. On day 60, 30 min after installation: tear ferning patterns changed from 100% pathological (types III-IV) to 93% physiological (types I-II) in the 0.4% HHA group and from 100% pathological to 78% physiological in the 0.3% HPMC group (p < 0.01 between groups). Tear osmolarity shifted from 353 +/- 23 to 305 +/- 6 mosmol/l in the 0.4% HHA group and from 346 +/- 15 to 336 +/- 8 mosmol/l in the 0.3% HPMC group (p < 0.001 between groups). On day 90, the impression cytology score improved from 1.2 to 1.9 in the 0.4% HHA group while it did not change in the 0.3% HPMC group (p < 0.05 between groups). CONCLUSION: In KCS appropriate treatment with a hypotonic 0.4% HHA tear substitute can change the tear environment and results in improvement of the epithelial conditions of the ocular surface.

Adjuvants, Immunologic↗

Isolated, unilateral, reversible palsy of the hypoglossal nerve.

We report three patients with isolated unilateral hypoglossal nerve palsy who experienced an excellent outcome. In two patients no cause was found. Our study seems to confirm that the occurrence of benign and idiopathic isolated unilateral palsy of the hypoglossal nerve is more frequent than previously reported. We would like to stress that neuroimaging studies remain mandatory in order to exclude other common causes, such as tumour and spontaneous or traumatic vascular lesions, in which a specific treatment is necessary.

Adolescent↗

Memory disturbances in migraine with and without aura: a strategy problem?

Cognitive defects in migraine have been reported by several authors. These findings however, are controversial. In this study we carried out an investigation on 14 patients with migraine with aura and 16 with migraine without aura according to the International Headache Society criteria. They were submitted to a comprehensive battery of neuropsychological tests. The patients were compared with a control group not significantly different as to age, sex and education. Migraine subjects showed impaired neuropsychological performances only on some cognitive tests. Both groups of patients did worse than the control group on visuo-spatial memory tasks, while only migraineurs without aura showed significantly impaired verbal memory performances. The memory defects, both on visuo-spatial and on verbal cognitive tasks, could depend on an impaired recall mechanism. These memory difficulties seem related to strategically and organizationally defective aspects of learning.

Adult↗

Prevalence of stroke : a door-to-door survey in rural Bolivia.

BACKGROUND AND PURPOSE: We carried out a door-to-door survey in rural areas of the Cordillera Province, Santa Cruz Department, Bolivia. A cluster sample of 10 124 inhabitants was selected, and 9955 subjects were screened. The aim was to determine the prevalence of the most common neurological diseases (epilepsy, stroke, parkinsonism, and peripheral neuropathy) in this population. METHODS: We used a modified version of the World Health Organization screening instrument. On screening we found that 1130 subjects tested positive, and 1027 underwent a complete neurological examination. According to the World Health Organization guidelines, we defined stroke as "rapidly developing clinical signs of focal (or global) disturbance of cerebral functions, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin." We considered only first stroke and excluded a possible stroke. RESULTS: We found 16 subjects (cases) who had experienced 1 complete stroke on prevalent day (November 1, 1994). The crude prevalence of stroke was 174/100 000 (322/100 000 age-adjusted to the world standard population) and 663/100 000 in subjects aged >/=35 years. Prevalence was >2-fold higher in men than in women (247/100 000 and 99/100 000, respectively) and increased rapidly with age. Seven cases were hospitalized and received specific treatment. CONCLUSIONS: Our crude prevalence is lower compared with rates from developed countries, probably because of a high case fatality rate. Our findings are comparable with those reported from other surveys carried out in rural developing countries.

Adolescent↗

Molecular mechanisms of photosensitization XIII: a combined differential scanning calorimetry and DNA photosensitization study in non steroidal antiinflammatory drugs-DNA interaction.

A combined differential scanning calorimetry (DSC) and photosensitization study has been carried out on the interaction of several NSAID on DNA, both from calf thymus and pBR 322 plasmid. The investigated compounds were both non-steroidal anti-inflammatory drugs as well as compounds related to NSAIDs for structural similar properties, to find evidence for their ability to interact with DNA as a function of steric hindrance and polarity of the chemical structures. The considered NSAIDs were diflunisal (DFN, a salicylic derivative), naproxen (NAP), ketoprofen (KPF), suprofen (SPF) and tiaprofenic acid (TIA, arylpropionic acids). The structural criterion used was related to three different aromatic groups, biphenyl, naphthalene and benzophenone (BZP). In fact drug-DNA interaction can be revealed by variations of the enthalpies and temperatures of unfolding of DNA obtained by comparison of calorimetric peaks, where a decrease of the enthalpy is associated with the drug-DNA interaction, by engaging electrostatic bonds. Testing their ability in inducing DNA cleavage when UVA irradiated can evidence the photosensitizing properties of the drug. A good correlation was found between calorimetric and photosensitization studies. From the results obtained it can be reasonably supposed that the photocleavage depends only on the drug molecules bound to DNA.

Animals↗

Supratentorial atrophy in spinocerebellar ataxia type 2: MRI study of 20 patients.

There have been only few studies of brain magnetic resonance imaging (MRI) in spinocerebellar ataxia (SCA) type 2. We investigated 20 SCA2 patients, from 11 Sicilian families, and 20 age-matched control subjects using MRI. Our data confirm that olivopontocerebellar atrophy (OPCA) is the typical pattern in SCA2. We found no significant correlation between infratentorial atrophy, disease duration, or the number of CAG repeats in our SCA2 patients, but there was supratentorial atrophy in 12 patients, with a significant correlation between supratentorial atrophy and disease duration. OPCA appears to represent the "core" of the SCA2: however, central nervous system involvement is not limited to pontocerebellar structures. We therefore consider central nervous system degeneration in SCA2 as a widespread atrophy. MRI is helpful in diagnosing SCA, but it is not diagnostic in the absence of clinical and molecular studies. We suggest that serial MRI may play a role in evaluating "in vivo" the progressive steps of neurodegeneration in SCA2, for a better comprehension of the pathophysiology of this disorder.

Adult↗

Spinocerebellar ataxia type 2 in southern Italy: a clinical and molecular study of 30 families.

Autosomal dominant cerebellar ataxia type I is the most common form of dominant ataxia. A genetic heterogeneity has been identified with five different loci (SCA1, 2, 3, 4, and 6). A pathological expansion of a CAG sequence has been identified in SCA1, 2, 3, and 6. We performed molecular analysis in 51 families with autosomal dominant cerebellar ataxia type I, mainly originating from southern Italy and Sicily. Thirty families carry an expanded CAG sequence within SCA2 gene. The mean number of repeats was 39.9 +/- 3.3 in 85 expanded alleles, with a range of 34-52. The number of triplets was inversely correlated with age at onset and explained 76% of the variance. The best fit was obtained with an exponential relationship between variables. Expanded alleles were unstable when transmitted from parents to offspring. Expansions were more common than contractions, accounting for 59% of the total meioses and for 80% of the father-child transmissions. The mean intergenerational variation was 1.9 repeats (range -3 to +15) with higher values for male transmissions. Bulbar and autonomic signs were related to disease duration, pyramidal signs to CAG size, cerebellar features and peripheral neuropathy to both. Among the remaining 21 families, three carried the SCA1 and one the SCA6 mutation. This study suggests that SCA2 is the prevalent mutation in southern Italy.

Adolescent↗

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↗

Phototoxicity of naphazoline. Evidence that hydrated electrons, nitrogen-centered radicals, and OH radicals trigger DNA damage: a combined photocleavage and laser flash photolysis study.

The potential phototoxic activity of naphazoline (NP), 2-(1-naphthylmethyl)imidazoline, was investigated by studying its photoreactivity toward DNA. Photocleavage studies combined with laser flash photolysis experiments provide clear evidence that the transient species produced under NP photolysis react with DNA, thereby promoting its breakage under both aerobic and anaerobic conditions. Hydrated electrons and nitrogen-centered radicals are involved in the photodamage under anaerobic conditions. Hydroxyl radicals generated by Haber-Weiss reaction seem to initiate the photocleavage observed under aerobic conditions. A photodynamic mechanism involving the participation of singlet oxygen does not seem to play a crucial role in the photoinduced DNA breakage. The interaction between the NP and the biopolymer is also investigated by using both steady state and time-resolved spectroscopy.

Algorithms↗