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Biomedical subjects

G Barone

Publications and source records attributed to G Barone.

At least 19 recordsLinked to original sources
PubMed2006

Safety and efficacy of fentanyl administered by patient controlled analgesia in children with cancer pain.

BACKGROUND: Pain is the most common discomfort experienced by children with cancer and occurs in almost 89% of patients in an advanced stage of the disease. It is most often not adequately treated because of inexperience and unfounded fears of analgesic treatment. In adults, patient controlled analgesia (PCA) is widely administered, while in children with moderate to severe cancer pain its use is still under evaluation for safety and efficacy. GOALS OF WORK: To evaluate the efficacy and safety of fentanyl administered by PCA in children with cancer pain. MATERIALS AND METHODS: Eighteen children (range 6 to 15 years) with moderate to severe pain were enrolled and treated with fentanyl by PCA plus background infusion (BI) (BI of 1 microg/kg/h with booster doses of 1 microg/kg by intravenous route). To evaluate efficacy and safety of the analgesic treatment, different subjective and objective parameters were monitored at 4-h intervals. In addition, patients' satisfaction was assessed by a questionnaire at the end of the treatment. MAIN RESULTS: All children experienced a good degree of analgesia and did not require any other analgesic drug during the treatment. Both subjective and objective parameters improved after starting pain-relieving treatment and no major side effects occurred. The questionnaire administered to the children showed a high grade of satisfaction. CONCLUSIONS: PCA plus BI with fentanyl administered by intravenous route is a safe and efficacious method for analgesia in children with moderate to severe cancer pain. Our policy of fentanyl-treatment did not show any major side effects.

Adolescent↗
PubMed2005

Concentrations and composition of organochlorine contaminants in different species of cephalopod molluscs from the Italian waters (Adriatic Sea).

Persistent organochlorines, such as polychlorinated biphenyls including coplanar congeners and DDT compounds were measured in the liver of different species of mollusc cephalopods: broadtail squid (Illex coindetii), horned octopus (Eledone moschata) and spider octopus (Octopus salutii) collected in two different areas of the Adriatic Sea (central and southern Adriatic Sea). The concentration of PCBs exceeded DDT ones in horned octopus (PCBs: 617.0 ngg(-1) lipid weight, DDTs: 188.0 ngg(-1) lipid weight) and in spider octopus (PCBs: 590.0 ngg(-1) lipid weight, DDTs: 293.0 ngg(-1) lipid weight), while in broadtail squid PCB load (748.0 ngg(-1) lipid weight) was similar to those of DDTs (514.5 ngg(-1) lipid weight). No significant difference in PCB levels was observed among species, while DDT concentrations were higher in broadtail squid than in horned octopus and spider octopus. DDTs composition showed slight differences in relation to species, thought p,p'-DDE was the predominant compound in all cephalopod species (broadtail squid: 88.1%, horned octopus 94.1%, spider octopus: 97.5%). PCB isomer profiles were similar among species being hexachlorinated isomers the most abundant, followed by penta- and heptachlorobiphenyls, while tri- and tetrachlorobiphenyls made up a small percentage of the total PCB residues. Regarding coplanar congeners, non-ortho PCBs were below the detection limit in all samples and the 2,3,7,8-TCDD toxic equivalent (TEQ) concentrations were very low. The influence of biological and ecological factors (size/weight and location) on the bioaccumulation of organochlorine compounds has been discussed.

Animals↗
PubMed2005

Quadruplex-forming oligonucleotides as tools in anticancer therapy and aptamers design: energetic aspects.

Recent investigations on the G-quadruplex motif propose a new strategy for the making of antitumour drugs. Quadruplex-drug complexes have been suggested to inhibit telomerase activity; further, aptamers based on the quadruplex motif have been proved useful as tools aimed at binding and inhibiting particular proteins, thus serving as pharmaceutically active agents. However, the design of new aptamers is difficult because many factors affecting their activity and stability have not still been clarified. The knowledge of the energetics of quadruplex formation is a crucial point in view of their potential therapeutic utilization both as targets as well as therapeutic agents. In this review the energetic aspects of both quadruplex assembly and quadruplex-ligand interactions are discussed together with a summary of recent studies on physico-chemical properties in solution of quadruplex structures obtained from synthetic aptamers, including PNA-DNA chimeras.

Animals↗
PubMed2005

Cadmium in cephalopod molluscs: implications for public health.

Cadmium concentrations were measured in the flesh and hepatopancreas (digestive gland) of 1,392 specimens of different species of cephalopod molluscs (broadtail squid, spider octopus, curled octopus, horned octopus, elegant cuttlefish, and pink cuttlefish) to determine whether maximum levels fixed by the European Commission were exceeded. In all species, mean cadmium concentrations were higher in hepatopancreas than in flesh. Large differences among the different species were also observed. Pink cuttlefish and spider octopus had the highest concentrations for both flesh (spider octopus, 0.77 microg g(-1); pink cuttlefish, 0.87 microg g(-1)) and hepatopancreas (spider octopus, 9.65 microg g(-1); pink cuttlefish, 18.03 microg g(-1)), and the lowest concentrations were encountered in broadtail squid (flesh, 0.13 microg g(-1); hepatopancreas, 2.48 microg g(-1)). The other species had intermediate concentrations of 0.20 to 0.30 microg g(-1) in flesh and 5.46 to 8.01 microg g(-1) in hepatopancreas. Concentrations exceeding the limit proposed by the European Commission (1.00 microg g(-1)) were observed in 44.4 and 40.0% of flesh samples of spider octopus and pink cuttlefish, respectively. The estimated weekly intake, 0.09 to 0.66 microg/kg body weigh, was below the provisional tolerable weekly intake set by the World Health Organization.

Animals↗
PubMed2004

Analysis of thermal adaptation in the HSL enzyme family.

The recently solved three-dimensional (3D) structures of two thermostable members of the carboxylesterase/lipase HSL family, namely the Alicyclobacillus (formerly Bacillus) acidocaldarius and Archaeoglobus fulgidus carboxylesterases (EST2 and AFEST, respectively) were compared with that of the mesophilic homologous counterpart Brefeldine A esterase from Bacillus subtilis. Since the 3D homology models of other members of the HSL family were also available, we performed a structural alignment with all these sequences. The resulting alignment was used to assess the amino acid "traffic rule" in the HSL family. Quite surprisingly, the data were in very good agreement with those recently reported from two independent groups and based on the comparison of a huge number of homologous sequences from the genus Bacillus, Methanococcus and Deinococcus/Thermus. Taken as a whole, the data point to the statistical meaning of defined amino acid conversions going from psychrophilic to hyperthermophilic sequences. We identified and mapped several such changes onto the EST2 structure and observed that such mutations were localized mostly in loops regions or alpha-helices and were mostly excluded from the active site. A site-directed mutagenesis of two of the identified residues confirmed they were involved in thermal stability.

Adaptation, Physiological↗
PubMed2004

Targeting duplex DNA with DNA-PNA chimeras? Physico-chemical characterization of a triplex DNA-PNA/DNA/DNA.

Targeting double-stranded DNA with homopyrimidine PNAs results in strand displacement complexes PNA/DNA/PNA rather than PNA/DNA/DNA triplex structures. Not much is known about the binding properties of DNA-PNA chimeras. A 16-mer 5'-DNA-3'-p-(N)PNA(C) has been investigated for its ability to hybridize a complementary duplex DNA by DSC, CD, and molecular modeling studies. The obtained results showed the formation of a triplex structure having similar, if not slightly higher, stability compared to the same all-DNA complex.

Chemical Phenomena↗
PubMed2004

Polychlorinated biphenyl residues in deep-sea fish from Mediterranean Sea.

Polychlorinated biphenyls including coplanar congeners were measured in the liver of different species of skates and ghostsharks. The mean concentrations of PCBs in skates (314 ng/g wet wt) were comparable with those in ghostsharks (285 ng/g wet wt). The specific analysis of PCB congeners in skates hepatic tissue revealed a profile dominated by hexa-, penta-, and heptachlorinated congeners followed by trichlorobiphenyls, tetra- and decachlorobiphenyls. A different profile dominated by hexa-, tri-, and pentachlorinated congeners, followed by heptachlorobiphenyl and decachlorobiphenyls was found in ghostsharks liver. The estimated 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) of coplanar PCBs in skates and ghostsharks were 0.48 and 0.33 pg/g wet weight, respectively, with mono-ortho congeners PCB105, 118 and 156 contributing more than 90% to the TEQs.

Animals↗
PubMed2004

Effects of the selective estrogen receptor modulator LY117018 on growth hormone secretion: In vitro studies.

Sex steroids play an important role in modulating pulsatile growth hormone (GH) release, acting at both hypothalamic and pituitary level in both humans and experimental animals. Selective estrogen receptor modulators (SERMs) act as either estrogen receptor agonists or antagonists in a tissue-selective manner. In postmenopausal women, serum GH levels correlate positively with endogenous estradiol levels and insulin-like grwoth factor-I (IGF-I) is positively related to bone mineral density (BMD) at the spine and hip. The aim of the present study was to evaluate, for the first time, the direct effect of LY117018, an analog of raloxifene, on GH secretion from both human and rodent pituitary cells in vitro. Our results demonstrated that pharmacological concentrations of the raloxifene analog LY117018 can stimulate GH secretion through a direct action on the pituitary. LY117018 also showed an estrogen-like activity, inducing the proliferation of rat pituitary GH-secreting adenomatous cells (GH1).

Adenoma↗
PubMed2003

Physico-chemical studies of a DNA triplex containing a new ferrocenemethyl-thymidine residue in the third strand.

The stability of a 16-mer DNA triple helix containing a 3-N(ferrocenemethyl)-thymidine residue in the third strand has been investigated in comparison with the unmodified triplex of the same sequence. A complete physico-chemical characterization of the two triple helices on changing the pH by means of calorimetry, circular dichroism and molecular modeling is therefore reported. The thermodynamic parameters were obtained in the pH range 5.5-7.2 by differential scanning calorimetry (DSC). For both triplexes the T(m) and Delta H degrees (T(m)) values increase on decreasing the pH. In the pH range 7.2-6.0 the triplex containing the ferrocenemethyl nucleoside is less stable than the unmodified one, whereas the modified triplex becomes more stable at pH 5.5. Such difference in stability at each pH value is overwhelmingly enthalpic in origin. CD spectra show conformational changes on decreasing the pH for both the triplexes. By spectroscopic pH titration the apparent pK(a) values of the cytosines in the two triplexes could be estimated, with the cytosines in the TFO containing the ferrocenemethyl residue having lower apparent pK(a) values. These results are consistent with the calorimetric data, showing a decrease of the thermodynamic parameters in the pH range 7.2-6.0 and an increase at pH 5.5 for the ferrocenylated triplex with respect to the unmodified one. The thermodynamic and spectroscopic data are also discussed in relation to molecular models.

Calorimetry, Differential Scanning↗
PubMed2003

Surgical management of ruptured aneurysms in the eighth and ninth decades.

BACKGROUND: The surgical management of elderly patients with aneurysmal subarachnoid haemorrhage (SAH) is controversial. The present study was performed to more clearly define issues facing elderly SAH patients undergoing surgical repair of their aneurysms. METHOD: Between 1990 and 2000, 100 patients, aged 70 years or older, were managed consecutively with aneurysmal surgical repair at Verona City Hospital. Ninety-seven of these were analysed with regard to age, clinical grade on admission, radiological features, and specific management components (3 patients were excluded from further analysis because of inadequate follow up data). Surviving patients were followed up for a minimum of 6 months and clinical outcome was assessed. FINDINGS: Hydrocephalus requiring permanent CSF diversion occurred in 44% of cases surviving beyond 10 days from their SAH. The development of hydrocephalus requiring shunting was delayed more than 6 weeks in 7% of these cases. Medical complications occurred in 22% of cases. Clinical grade of haemorrhage (p<0.001), early hydrocephalus requiring ventriculostomy (p=0.003) and the development of medical complications (p=0.03) were significantly associated with poor outcome. Clinical vasospasm was not a major determinant of outcome in this group. The need for permanent CSF diversion was significantly associated with increasing age (p=0.03), intraventricular haemorrhage (p<0.001), early hydrocephalus requiring ventriculostomy (p=0.003) and the development of medical complications (p=0.05). INTERPRETATION: Elderly patients experience a different range of complications following aneurysmal subarachnoid haemorrhage than their younger counterparts. Clinicians should remain alert to the development of hydrocephalus, especially of delayed onset.

Age Factors↗
PubMed2001

Thermodynamic and computational studies of DNA triple helices containing a nucleotide or a non-nucleotide linker in the third strand.

In this paper we report a thermodynamic characterisation of stability and melting behaviour of four different triple helices at pH 6.0. The target duplex consists of 16 base pairs in alternate sequence of the type 5'-(purine)(m)(pyrimidine)(m)-3'. The four triplexes are formed by targeting the 16-mer duplex with an all pyrimidine 16-mer or 15-mer or 14-mer third strand. The 16-mer oligonucleotide contains a 3'-3' phosphodiester junction and corresponding triplex was named 16-mer P. The 14-mer oligonucleotide contains a non-nucleotide linker, the 1,2,3 propanetriol residue and the corresponding triplex was named 14-mer PT. For the 15-mer oligonucleotide both junctions were alternatively used and the relative triplexes were named 15-mer P and 15-mer PT, respectively. These linkers introduce the appropriate polarity inversion and let the third strand switch from one oligopurine strand of the duplex to the other. Thermal denaturation profiles indicate the initial loss of the third strand followed by the dissociation of the target duplex. Transition enthalpies, entropies and free energies were derived from differential scanning calorimetric measurements. The comparison of Gibbs energies reveals that a more stable triplex is obtained when in the third strand there is the lack of one nucleotide in the junction region and a propanetriol residue as linker was used. The thermodynamic data were discussed in light of molecular mechanics and dynamics calculations.

Calorimetry, Differential Scanning↗
PubMed2001

A 23Na NMR study of the effect of D(+) and L(-) arabitol on NaDNA in aqueous solution.

The 23Na NMR quadrupolar relaxation in NaDNA aqueous solutions has been investigated in the presence of D(+) and L(-) arabitol. Quite different results were produced by the enantiomers, i.e. the addition of D(+) arabitol produced a small increase of the 23Na NMR relaxation rates, while in the presence of L(-) arabitol a significant decrease was observed. These findings were analysed and discussed in terms of an effective interaction of L(-) arabitol with DNA.

Animals↗
PubMed2001

Contribution of chain termini to the conformational stability and biological activity of onconase.

Onconase, a member of the RNase A superfamily, is a potent antitumor agent which is undergoing phase III clinical trials as an antitumor drug. We have recently shown that onconase is an unusually stable protein. Furthermore, the protein is resistant to the action of proteases, which could influence its use as a drug, prolonging its biological life, and leading to its renal toxicity. Our investigation focused on the contribution of chain termini to onconase conformational stability and biological activities. We used differential scanning calorimetry, isothermal unfolding experiments, limited proteolysis, and catalytic and antitumor activity determinations to investigate the effect of the elimination of the two blocks at the chain termini, the N-terminal cyclized glutamine and the C-terminal disulfide bridge between the terminal Cys104 and Cys87. The determination of the thermodynamic parameters of the protein led to the conclusion that the two blocks at onconase chain termini are responsible for the unusual stability of the protein. Moreover, the reduced stability of the onconase mutants does not influence greatly their catalytic and antitumor activities. Thus, our data would suggest that an onconase-based drug, with a decreased toxicity, could be obtained through the use of less stable onconase variants.

3T3 Cells↗
PubMed2001

Physico-chemical studies on DNA triplexes containing an alternate third strand with a non-nucleotide linker.

Differential scanning calorimetric (DSC), circular dichroism (CD) and molecular mechanics studies have been performed on two triple helices of DNA. The target duplex consists of 16 base pairs in alternate sequence of the type 5'-(purine)m(pyrimidine)m-3'. In both the triplexes, the third oligopyrimidine strand crosses the major groove at the purine-pyrimidine junction, with a simultaneous binding of the adjacent purine tracts on alternate strands of the Watson-Crick duplex. The switch is ensured by a non-nucleotide linker, the 1,2,3 propanetriol residue, that joins two 3'-3' phosphodiester ends. The third strands differ from each other for a nucleotide in the junction region. The resulting triple helices were termed 14-mer-PXP and 15-mer-PXP (where P = phosphate and X = 1,2,3-propanetriol residue) according to the number of nucleotides that compose the third strand. DSC data show two independent processes: the first corresponding to the dissociation of the third strand from the target duplex, the second to the dissociation of the double helix in two single strands. The two triple helices show the same stability at pH 6.6. At pH 6.0, the 15-mer-PXP triplex is thermodynamically more stable than the 14-mer-PXP triplex. Thermodynamic data are discussed in relation to structural models. The results are useful when considering the design of oligonucleotides that can bind in an antigene approach to the DNA for therapeutic purposes.

Base Composition↗
PubMed2000

Onconase: an unusually stable protein.

Several members of the RNase A superfamily are endowed with antitumor activity, showing selective cytotoxicity toward tumor cell lines. One of these is onconase, the smallest member of the superfamily, which at present is undergoing phase-III clinical trials as an antitumor drug. Our investigation focused on other interesting features of the enzyme, such as its unusually high denaturation temperature, its low catalytic activity, and its renal toxicity as a drug. We used differential scanning calorimetry, circular dichroism, fluorescence measurements, and limited proteolysis to investigate the molecular determinants of the stability of onconase and of a mutant, (M23L)-ONC, which is catalytically more active than the wild-type enzyme, and fully active as an antitumor agent. The determination of the main thermodynamic parameters of the protein led to the conclusion that onconase is an unusually stable protein. This was confirmed by its resistance to proteolysis. On the basis of this analysis and on a comparative analysis of the (M23L)-ONC variant of the protein, which is less stable and more sensitive to proteolysis, a model was constructed in line with available data. This model supports a satisfactory hypothesis of the molecular basis of onconase stability and low-catalytic activity.

Amino Acid Substitution↗
PubMed2000

Thermodynamic stability of the two isoforms of bovine seminal ribonuclease.

Bovine seminal ribonuclease (BS-RNase) is a dimeric protein with two identical subunits linked by two disulfide bridges, each subunit showing 80% of sequence identity with pancreatic RNase A. BS-RNase exists in two different quaternary conformations in solution: the MxM form, in which each subunit exchanges its alpha-helical N-terminal segment with its partner, and the M=M form with no exchange. By differential scanning microcalorimetry (DSC), the denaturation of the two dimeric forms of BS-RNase was found to be more complex than a simple two-state process. Monomeric derivatives of the dimeric protein follow instead a simple two-state mechanism, but are distinctly less stable than RNase A. The three-state N if I if D denaturation process of the two quaternary isoforms was interpreted by identifying in the dimers a central highly structured core, enclosing the covalently bonded subunit interface, which unfolds only after the periphery (mainly the N-terminal peptide) unfolds. Circular dichroism spectra of the two forms in the far-ultraviolet region show large differences between the secondary structure of the isoforms and that of the native BS-RNase mixture at equilibrium. This has been attributed to the presence in the equilibrium mixture of intermediate forms with displaced and disordered N-terminal alpha-helical segments.

Animals↗