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Showing papers by "University of Cagliari published in 2004"


Journal ArticleDOI
TL;DR: This work identifies the nature of the ferroelectric phase transition in the hexagonal manganite, YMnO3, using a combination of single-crystal X-ray diffraction, thorough structure analysis and first-principles density-functional calculations, and suggests an avenue for designing novel magnetic ferroelectrics.
Abstract: Understanding the ferroelectrocity in magnetic ferroelectric oxides is of both fundamental and technological importance. Here, we identify the nature of the ferroelectric phase transition in the hexagonal manganite, YMnO3, using a combination of single-crystal X-ray diffraction, thorough structure analysis and first-principles density-functional calculations. The ferroelectric phase is characterized by a buckling of the layered MnO5 polyhedra, accompanied by displacements of the Y ions, which lead to a net electric polarization. Our calculations show that the mechanism is driven entirely by electrostatic and size effects, rather than the usual changes in chemical bonding associated with ferroelectric phase transitions in perovskite oxides. As a result, the usual indicators of structural instability, such as anomalies in Born effective charges on the active ions, do not hold. In contrast to the chemically stabilized ferroelectrics, this mechanism for ferroelectricity permits the coexistence of magnetism and ferroelectricity, and so suggests an avenue for designing novel magnetic ferroelectrics.

1,042 citations


Journal ArticleDOI
TL;DR: It is speculated that drug addiction results from the impact exerted on behavior by the abnormal DA stimulant properties acquired by drug-conditioned stimuli as a result of their association with addictive drugs.

880 citations


Journal ArticleDOI
20 Feb 2004-Science
TL;DR: The detection of the 2.8-second pulsar J0737–3039B as the companion to the 23-millisecond pulsars in a highly relativistic double neutron star system, allowing unprecedented tests of fundamental gravitational physics.
Abstract: The clocklike properties of pulsars moving in the gravitational fields of their unseen neutron-star companions have allowed unique tests of general relativity and provided evidence for gravitational radiation. We report here the detection of the 2.8-second pulsar J07373039B as the companion to the 23-millisecond pulsar J07373039A in a highly relativistic double neutron star system, allowing unprecedented tests of fundamental gravitational physics. We observed a short eclipse of J07373039A by J07373039B and orbital modulation of the flux density and the pulse shape of J07373039B, probably because of the influence of J07373039A’s energy flux on its magnetosphere. These effects will allow us to probe magneto-ionic properties of a pulsar magnetosphere. Double neutron star (DNS) binaries are rare, and only six such systems are known. How

829 citations


Journal ArticleDOI
TL;DR: A general scheme for practice in Europe could be provided and a set of recommendations for the conceptualisation and management of hyperkinetic disorder and attention deficit/hyperactivity disorder (ADHD) are presented.
Abstract: BACKGROUND: The validity of clinical guidelines changes over time, because new evidence-based knowledge and experience develop OBJECTIVE: Hence, the European clinical guidelines on hyperkinetic disorder from 1998 had to be evaluated and modified METHOD: Discussions at the European Network for Hyperkinetic Disorders (EUNETHYDIS) and iterative critique of each clinical analysis Guided by evidence-based information and based on evaluation (rather than metaanalysis) of the scientific evidence a group of child psychiatrists and psychologists from several European countries updated the guidelines of 1998 When reliable information is lacking the group gives a clinical consensus when it could be found among themselves RESULTS: The group presents here a set of recommendations for the conceptualization and management of hyperkinetic disorder and attention deficit/hyperactivity disorder (ADHD) CONCLUSION: A general scheme for practice in Europe could be provided, on behalf of the European Society for Child and Adolescent Psychiatry (ESCAP)

652 citations


Journal ArticleDOI
TL;DR: The results indicate that the two pathways work in a cooperative manner to release endocannabinoids in the VTA, where they play a role as retrograde messengers for DSE via CB1-Rs.
Abstract: The endogenous cannabinoid system has been shown to play a crucial role in controlling neuronal excitability and synaptic transmission. In this study we investigated the effects of a cannabinoid receptor (CB-R) agonist WIN 55,212-2 (WIN) on excitatory synaptic transmission in the rat ventral tegmental area (VTA). Whole-cell patch clamp recordings were performed from VTA dopamine (DA) neurons in an in vitro slice preparation. WIN reduced both NMDA and AMPA EPSCs, as well as miniature EPSCs (mEPSCs), and increased the paired-pulse ratio, indicating a presynaptic locus of its action. We also found that WIN-induced effects were dose-dependent and mimicked by the CB1-R agonist HU210. Furthermore, two CB1-R antagonists, AM281 and SR141716A, blocked WIN-induced effects, suggesting that WIN modulates excitatory synaptic transmission via activation of CB1-Rs. Our additional finding that both AM281 and SR141716A per se increased NMDA EPSCs suggests that endogenous cannabinoids, released from depolarized postsynaptic neurons, might act retrogradely on presynaptic CB1-Rs to suppress glutamate release. Hence, we report that a type of synaptic modulation, previously termed depolarization-induced suppression of excitation (DSE), is present also in the VTA as a calcium-dependent phenomenon, blocked by both AM281 and SR141716A, and occluded by WIN. Importantly, DSE was partially blocked by the D2DA antagonist eticlopride and enhanced by the D2DA agonist quinpirole without changing the presynaptic cannabinoid sensitivity. These results indicate that the two pathways work in a cooperative manner to release endocannabinoids in the VTA, where they play a role as retrograde messengers for DSE via CB1-Rs.

442 citations


Journal ArticleDOI
TL;DR: The phylogeography of Y-chromosome haplogroups E and J was investigated in >2400 subjects from 29 populations, mainly from Europe and the Mediterranean area but also from Africa and Asia, revealing spatial patterns that are consistent with a Levantine/Anatolian dispersal route to southeastern Europe.
Abstract: The phylogeography of Y-chromosome haplogroups E (Hg E) and J (Hg J) was investigated in >2,400 subjects from 29 populations, mainly from Europe and the Mediterranean area but also from Africa and Asia. The observed 501 Hg E and 445 Hg J samples were subtyped using 36 binary markers and eight microsatellite loci. Spatial patterns reveal that (1) the two sister clades, J-M267 and J-M172, are distributed differentially within the Near East, North Africa, and Europe; (2) J-M267 was spread by two temporally distinct migratory episodes, the most recent one probably associated with the diffusion of Arab people; (3) E-M81 is typical of Berbers, and its presence in Iberia and Sicily is due to recent gene flow from North Africa; (4) J-M172(xM12) distribution is consistent with a Levantine/Anatolian dispersal route to southeastern Europe and may reflect the spread of Anatolian farmers; and (5) E-M78 (for which microsatellite data suggest an eastern African origin) and, to a lesser extent, J-M12(M102) lineages would trace the subsequent diffusion of people from the southern Balkans to the west. A 7%–22% contribution of Y chromosomes from Greece to southern Italy was estimated by admixture analysis.

399 citations


Journal ArticleDOI
TL;DR: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen.
Abstract: OBJECTIVE: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. METHODS: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. RESULTS: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome. CONCLUSION: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.

323 citations


Journal ArticleDOI
TL;DR: In this article, the authors used a rigorous statistical method, which produces a coalescence rate for Galactic double neutron star (DNS) systems that is higher by a factor of 6-7 compared to estimates made prior to the discovery of the highly relativistic binary pulsar J07373039.
Abstract: We report on the newly increased event rates due to the recent discovery of the highly relativistic binary pulsar J07373039. Using a rigorous statistical method, we present the calculations reported by Burgay et al., which produce a coalescence rate for Galactic double neutron star (DNS) systems that is higher by a factor of 6–7 compared to estimates made prior to the new discovery. Our method takes into account known pulsar survey selection effects and biases due to small-number statistics. This rate increase has dramatic implications for gravitational wave detectors. For the initial Laser Interferometer Gravitational-Wave Observatory (LIGO) detectors, the most probable detection rates for DNS in-spirals are one event per 5–250 yr; at 95% confidence, we obtain rates up to one per 1.5 yr. For the advanced LIGO detectors, the most probable rates are 20–1000 events per year. These predictions, for the first time, bring the expectations for DNS detections by the initial LIGO detectors to the astrophysically relevant regime. We also use our models to predict that the large-scale Parkes Multibeam pulsar survey with acceleration searches could detect an average of three to four binary pulsars similar to those known at present. Subject headings: binaries: close — gravitational waves — methods: statistical — stars: neutron

314 citations


Journal ArticleDOI
TL;DR: The antimicrobial and antifungal tests showed a weak activity of Sardinian rosemary, and an inductive effect on fungal growth, especially toward Fusarium graminearum was observed.
Abstract: The chemical composition of the essential oil of the Sardinian Rosmarinus officinalis L. obtained by hydro distillation and steam\hydro distillation was studied using GC-FID and MS. Samples were collected at different latitude and longitude of Sardinia (Italy). The yields ranged between 1.75 and 0.48% (v/w, volume/dry-weight). A total of 30 components were identified. The major compounds in the essential oil were alpha-pinene, borneol, (-) camphene, camphor, verbenone, and bornyl-acetate. Multivariate analysis carried out on chemical molecular markers, with the appraisal of chemical, pedological, and random amplified polymorphic DNA data, allows four different clusters to be distinguished. The antimicrobial and antifungal tests showed a weak activity of Sardinian rosemary. On the other hand, an inductive effect on fungal growth, especially toward Fusarium graminearum was observed.

298 citations


Journal ArticleDOI
TL;DR: In this paper, a series of recommendations were put forward by the participants concerning definitions and notations for describing effects of intrinsic transversemomentum of partons in semi-inclusive deep inelastic scattering.
Abstract: During the workshop ``Transversity: New Developments in Nucleon Spin Structure'' (${\mathrm{E}\mathrm{C}\mathrm{T}}^{*}$, Trento, Italy, 14--18 June 2004), a series of recommendations was put forward by the participants concerning definitions and notations for describing effects of intrinsic transverse-momentum of partons in semi-inclusive deep inelastic scattering.

282 citations


Journal ArticleDOI
TL;DR: Comparison between different groups showed significant differences for age, Expanded Disability Status Scale, disease duration, and disease course, but not for sex, underlines the relevance of pain in the clinical history of MS.
Abstract: In a multicenter cross-sectional study, the authors assessed pain in patients with multiple sclerosis (MS) using a symptom-oriented approach. Out of 2,077 questionnaires, we used 1,672 for data analysis. Pain and frequencies included trigeminal neuralgia 2%, Lhermitte's sign 9%, dysesthetic pain 18.1%, back pain 16.4%, and painful tonic spasms 11%. Comparison between different groups showed significant differences for age, Expanded Disability Status Scale, disease duration, and disease course, but not for sex. This study underlines the relevance of pain in the clinical history of MS.

Journal ArticleDOI
TL;DR: High doses of interferon alpha-2a significantly improved the long-term clinical outcome and survival of patients with chronic hepatitis D, even though the majority had active cirrhosis before the onset of therapy.

Journal ArticleDOI
TL;DR: The efficacy and safety of peginterferon alfa-2a and ribavirin combination therapy in patients with chronic hepatitis C and persistently normal alanine aminotransferase (ALT) levels are similar to that in Patients with elevated ALT levels.

Journal ArticleDOI
TL;DR: This work shows that physiologically relevant patterns of synaptic activity induce a transient suppression of excitatory transmission onto dopamine neurons in vitro, and indicates that dopamine neurons release 2-AG to shape afferent activity and ultimately their own firing pattern.
Abstract: Endocannabinoids form a novel class of retrograde messengers that modulate short- and long-term synaptic plasticity. Depolarization-induced suppression of excitation (DSE) and inhibition (DSI) are the best characterized transient forms of endocannabinoid-mediated synaptic modulation. Stimulation protocols consisting of long-lasting voltage steps to the postsynaptic cell are routinely used to evoke DSE-DSI. Little is known, however, about more physiological conditions under which these molecules are released in vitro. Moreover, the occurrence in vivo of such forms of endocannabinoid-mediated modulation is still controversial. Here we show that physiologically relevant patterns of synaptic activity induce a transient suppression of excitatory transmission onto dopamine neurons in vitro. Accordingly, in vivo endocannabinoids depress the increase in firing and bursting activity evoked in dopamine neurons by prefrontal cortex stimulation. This phenomenon is selectively mediated by the endocannabinoid 2-arachidonoyl-glycerol (2-AG), which activates presynaptic cannabinoid type 1 receptors. 2-AG synthesis involves activation of metabotropic glutamate receptors and Ca2+ mobilization from intracellular stores. These findings indicate that dopamine neurons release 2-AG to shape afferent activity and ultimately their own firing pattern. This novel endocannabinoid-mediated self-regulatory role of dopamine neurons may bear relevance in the pathogenesis of neuropsychiatric disorders such as schizophrenia and addiction.

Journal ArticleDOI
TL;DR: The present study shows that earlier work based on fewer Y-chromosome markers led to rather simple historical interpretations and highlights the fact that many population-genetic analyses are not robust to a poorly resolved phylogeny and reveals signatures of several distinct processes of migrations and/or recurrent gene flow that occurred in Africa and western Eurasia over the past 25000 years.
Abstract: We explored the phylogeography of human Y-chromosomal haplogroup E3b by analyzing 3,401 individuals from five continents. Our data refine the phylogeny of the entire haplogroup, which appears as a collection of lineages with very different evolutionary histories, and reveal signatures of several distinct processes of migrations and/or recurrent gene flow that occurred in Africa and western Eurasia over the past 25,000 years. In Europe, the overall frequency pattern of haplogroup E-M78 does not support the hypothesis of a uniform spread of people from a single parental Near Eastern population. The distribution of E-M81 chromosomes in Africa closely matches the present area of distribution of Berber-speaking populations on the continent, suggesting a close haplogroup–ethnic group parallelism. E-M34 chromosomes were more likely introduced in Ethiopia from the Near East. In conclusion, the present study shows that earlier work based on fewer Y-chromosome markers led to rather simple historical interpretations and highlights the fact that many population-genetic analyses are not robust to a poorly resolved phylogeny.

Journal ArticleDOI
TL;DR: Three-month therapy with allopurinol improved FMD in hyperuricemic subjects, showing an intrinsic negative effect of elevated UA levels on the arterial wall; conversely, FMD remained unchanged in controls, thus suggesting that the reduction of UA to less than a certain value does not affect endothelial function.
Abstract: The aim of the present study was to evaluate the effect of increased serum uric acid (UA) levels and their therapeutic reduction with allopurinol on endothelium-dependent dilation in subjects with a high cardiovascular (CV) risk but who were free from clinical CV disease. Patients with hyperuricemia had impaired flow-mediated dilation (FMD) compared with matched controls with normal UA levels and elevated CV risk. Three-month therapy with allopurinol improved FMD in hyperuricemic subjects, showing an intrinsic negative effect of elevated UA levels on the arterial wall; conversely, FMD remained unchanged in controls, thus suggesting that the reduction of UA to less than a certain value does not affect endothelial function.

Journal ArticleDOI
TL;DR: It is shown that ethanol increases the concentration of 3α,5α-THP as well as the amplitude of GABAA receptor-mediated IPSCs recorded from CA1 pyramidal neurons in isolated hippocampal slices, suggesting that ethanol may modulate GabAA receptor function through an increase in de novo neurosteroid synthesis in the brain that is independent of the HPA axis.
Abstract: An interaction with the GABA type A (GABAA) receptor has long been recognized as one of the main neurochemical mechanisms underlying many of the pharmacological actions of ethanol. However, more recent data have suggested that certain behavioral and electrophysiological actions of ethanol are mediated by an increase in brain concentration of neuroactive steroids that results from stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. Neuroactive steroids such as 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP) are, in fact, potent and efficacious endogenous positive modulators of GABAA receptor function. Because neurosteroids can be synthesized de novo in the brain, we have investigated whether ethanol might affect both neurosteroid synthesis and GABAA receptor function in isolated rat hippocampal tissue. Here, we show that ethanol increases the concentration of 3α,5α-THP as well as the amplitude of GABAA receptor-mediated IPSCs recorded from CA1 pyramidal neurons in isolated hippocampal slices. These effects are shared by the neurosteroid precursor progesterone, the peripheral benzodiazepine receptor-selective agonist CB34, and γ-hydroxybutyrate, all of which are known to increase the formation of neuroactive steroids in plasma and in the brain. The action of ethanol on GABAA receptor-mediated IPSC amplitude is biphasic, consisting of a rapid, direct effect on GABAA receptor activity and an indirect effect that appears to be mediated by neurosteroid synthesis. Furthermore, ethanol affects GABAA receptor activity through a presynaptic action, an effect that is not dependent on neurosteroid formation. These observations suggest that ethanol may modulate GABAA receptor function through an increase in de novo neurosteroid synthesis in the brain that is independent of the HPA axis. This novel mechanism may have a crucial role in mediating specific central effects of ethanol.

Journal ArticleDOI
TL;DR: It is suggested that an enduring form of neuronal adaptation occurs in DA neurons after subchronic cannabinoid intake at a young age, affecting subsequent responses to drugs of abuse.

Journal ArticleDOI
TL;DR: The Parkes multibeam pulsar survey has led to the discovery of more than 700 radio pulsars as discussed by the authors, including two pulsars with rotational periods of less than 6 s and a third pulsar with a period of 1.8 ms.
Abstract: The Parkes multibeam pulsar survey has led to the discovery of more than 700 pulsars. In this paper, we provide timing solutions, flux densities and pulse profiles for 180 of these new discoveries. Two pulsars, PSRs J1736−2843 and J1847−0130, have rotational periods P > 6 s and are therefore among the slowest rotating radio pulsars known. Conversely, with P = 1.8 ms, PSR J1843−1113 has the third-shortest period of pulsars currently known. This pulsar and PSR J1905+0400 (P = 3.8 ms) are both solitary. We also provide orbital parameters for a new binary system, PSR J1420−5625, which has P = 34 ms, an orbital period of 40 d and a minimum companion mass of 0.4 solar masses. The 10 ◦ -wide strip along the Galactic plane that was surveyed is known to contain 264 radio pulsars that were discovered prior to the multibeam pulsar survey. We have redetected almost all of these pulsars and provide new dispersion measure values and flux densities at 20 cm for the redetected pulsars.

Journal ArticleDOI
TL;DR: The Parkes Multibeam Pulsar Survey (PMPS) as mentioned in this paper was the most successful survey of the Galactic plane ever performed, finding over 600 pulsars in the initial processing.
Abstract: The Parkes Multibeam Pulsar Survey is the most successful survey of the Galactic plane ever performed, finding over 600 pulsars in the initial processing. We report on a reprocessing of all 40 000 beams with a number of algorithms, including conventional frequency-domain searches and an acceleration search for fast binary pulsars. The very large volume of results coupled with the need to distinguish new candidates from known pulsars and their many harmonics, often with multiple detections from different search algorithms, necessitated the development of a new graphical selection tool tightly linked to a web-based results data base. We discuss and demonstrate the benefits of these software systems, which are specifically designed for large survey projects. The results of this processing have been encouraging. We have discovered 128 new pulsars, including 11 binary and 15 millisecond pulsars; in addition to those previously found in the survey, we have thus far discovered 737 pulsars. In this paper, we discuss the discoveries of PSR J1744-3922 (a 172-ms mildly recycled pulsar in a 4.6-h orbit that exhibits nulling behaviour, not previously observed in recycled or binary objects), PSR J1802-2124 (an intermediate mass binary pulsar) and PSR J1801-1417 (a solitary millisecond pulsar).

Journal ArticleDOI
TL;DR: Hepatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary to viral infection or iron overload, and patients affected by thalassaemia syndromes have a theoretically high risk of developing the tumour.
Abstract: Hepatocellular carcinoma (HCC) frequently complicates hepatic cirrhosis secondary to viral infection or iron overload. Therefore, patients affected by thalassaemia syndromes have a theoretically high risk of developing the tumour. We collected data on patients attending Italian centres for the treatment of thalassaemia. Twenty-two cases of HCC were identified; 15 were male. At diagnosis, the mean age was 45 +/- 11 years and the mean serum ferritin was 1764 +/- 1448 microg/l. Eighty-six percent had been infected by hepatitis C virus. Nineteen of 22 cases were diagnosed after 1993, suggesting that this problem is becoming more frequent with the aging population of thalassaemia patients.

Journal ArticleDOI
TL;DR: It is suggested that acetaldehyde, by increasing DA neuronal activity in the VTA, may significantly contribute to the centrally mediated positive motivational properties of ethanol, which would oppose the well-known peripherally originating aversive properties.

Journal ArticleDOI
TL;DR: In rats that developed dyskinesia, GABA neurons had an increased transcriptional activity, and genes involved in Ca2+ homeostasis, inCa2+ -dependent signaling, and in structural and synaptic plasticity were upregulated.

Journal ArticleDOI
TL;DR: A series of 3- and 5-methylthiophene-2-carboxaldehyde alpha-(N)-heterocyclichydrazones were synthesized and submitted to an in vitro investigation of their anticancer, anti-HIV and antimicrobial activities, where some of the newly synthesized compounds were found to possess antiproliferative properties.

Journal ArticleDOI
TL;DR: Findings show that paraventricular oxytocinergic neurons projecting to extrahypothalamic brain areas and to the spinal cord and the paravocentular nucleus play an important role in the control of erectile function and male sexual behaviour in mammals.

Journal ArticleDOI
TL;DR: A nonredundant role of VGF products in the regulation of energy storage and expenditure is implied, implying a non redundant roles in theregulation of energystorage and expenditure.
Abstract: 1. The vgf gene encodes a neuropeptide precursor with a restricted pattern of expression that is limited to a subset of neurons in the central and peripheral nervous systems and to specific populations of endocrine cells in the adenohypophysis, adrenal medulla, gastrointestinal tract, and pancreas. In responsive neurons, vgf transcription is upregulated by neurotrophins, the basis for the original identification of VGF as nerve growth factor- (NGF) inducible in PC12 cells (A. Levi, J. D. Eldridge, and B. M. Paterson, Science229:393–395, 1985).

Journal ArticleDOI
TL;DR: The results reveal that temporin L increases the permeability of the bacterial inner membrane in a dose-dependent manner without destroying the cell's integrity, in contrast with many antimicrobial peptides.
Abstract: Antimicrobial peptides are produced by all organisms in response to microbial invasion and are considered as promising candidates for future antibiotics. There is a wealth of evidence that many of them interact and increase the permeability of bacterial membranes as part of their killing mechanism. However, it is not clear whether this is the lethal step. To address this issue, we studied the interaction of the antimicrobial peptide temporin L with Escherichia coli by using fluorescence, confocal and electron microscopy. The peptide previously isolated from skin secretions of the frog Rana temporaria has the sequence FVQWFSKFLGRIL-NH2. With regard to fluorescence microscopy, we applied, for the first time, a triple-staining method based on the fluorochromes 5-cyano-2,3-ditolyl tetrazolium chloride, 4',6-diamidino-2-phenylindole and FITC. This technique enabled us to identify, in the same sample, both living and total cells, as well as bacteria with altered membrane permeability. These results reveal that temporin L increases the permeability of the bacterial inner membrane in a dose-dependent manner without destroying the cell's integrity. At low peptide concentrations, the inner membrane becomes permeable to small molecules but does not allow the killing of bacteria. However, at high peptide concentrations, larger molecules, but not DNA, leak out, which results in cell death. Very interestingly, in contrast with many antimicrobial peptides, temporin L does not lyse E. coli cells but rather forms ghost-like bacteria, as observed by scanning and transmission electron microscopy. Besides shedding light on the mode of action of temporin L and possibly that of other antimicrobial peptides, the present study demonstrates the advantage of using the triple-fluorescence approach combined with microscopical techniques to explore the mechanism of membrane-active peptides in general.

Journal ArticleDOI
TL;DR: The results suggest that the FtsA protein could also polymerize in vivo and the polymers participate in septation, consistent with the absence of an ATPase activity.
Abstract: We studied the cytological and biochemical properties of the FtsA protein of Streptococcus pneumoniae. FtsA is a widespread bacterial cell division protein that belongs to the actin superfamily. In Escherichia coli and Bacillus subtilis, FtsA localizes to the septal ring after FtsZ, but its exact role in septation is not known. In S. pneumoniae, we found that, during exponential growth, the protein localizes to the nascent septa, at the equatorial zones of the dividing cells, where an average of 2200 FtsA molecules per cell are present. Likewise, FtsZ was found to localize with the same pattern and to be present at an average of 3000 molecules per cell. Consistent with the colocalization, FtsA was found to interact with FtsZ and with itself. Purified FtsA is able to bind several nucleotides, the affinity being highest for adenosine triphosphate (ATP), and lower for other triphosphates and diphosphates. The protein polymerizes in vitro, in a nucleotide-dependent manner, forming long corkscrew-like helixes, composed of 2 + 2 paired protofilaments. No nucleotide hydrolytic activity was detected. Consistent with the absence of an ATPase activity, the polymers are highly stable and not dynamic. These results suggest that the FtsA protein could also polymerize in vivo and the polymers participate in septation.

Journal ArticleDOI
TL;DR: In this article, the authors describe the results of recent preclinical and clinical studies conducted in this laboratory in order to characterize the anti-alcohol properties of the GABA(B) receptor agonist, baclofen.
Abstract: The present paper describes the results of recent preclinical and clinical studies conducted in this laboratory in order to characterize the anti-alcohol properties of the GABA(B) receptor agonist, baclofen. At a preclinical level, the repeated administration of non-sedative doses of baclofen dose-dependently suppressed the acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage, 2-bottle "alcohol vs water" choice regimen. Acute injection of baclofen completely blocked the temporary increase in voluntary alcohol intake occurring after a period of alcohol abstinence (the so-called alcohol deprivation effect, which models alcohol relapses in human alcoholics). Acute treatment with baclofen also dose-dependently suppressed extinction responding for alcohol (an index of motivation to consume alcohol) in sP rats trained to lever-press for oral alcohol self-administration. Taken together, these results suggest the involvement of the GABA(B) receptor in the neural substrate mediating alcohol intake and alcohol motivational properties in an animal model of excessive alcohol consumption. Further, acutely administered baclofen dose-dependently reduced the severity of alcohol withdrawal signs in Wistar rats made physically dependent upon alcohol. Preliminary clinical surveys suggest that the anti-alcohol properties of baclofen observed in rats may generalize to human alcoholics. Indeed, a double-blind survey demonstrated that repeated daily treatment with baclofen was associated, when compared to placebo, with a higher percentage of subjects totally abstinent from alcohol and a higher number of days of total abstinence. Treatment with baclofen also suppressed the number of daily drinks and decreased the obsessive and compulsive components of alcohol craving. Finally, a single non-sedative dose of baclofen resulted in the rapid disappearance of alcohol withdrawal symptomatology, including delirium tremens, in alcohol-dependent patients. In both clinical studies, baclofen was well tolerated with minimal side effects. These results suggest that baclofen may represent a potentially effective medication in the treatment of alcohol-dependent patients.

Journal Article
TL;DR: The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life.
Abstract: Objective: Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease. Patients and Methods: On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n − 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with α-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: ( a ) clinical variables (stage and Eastern Cooperative Oncology Group performance status); ( b ) nutritional variables (lean body mass, appetite, and resting energy expenditure); ( c ) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and ( d ) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress. Results: As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-α decreased significantly. As for quality of life, it comprehensively improved after treatment. Conclusions: The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life. The treatment has been shown to be safe with good compliance of patients. The study is in progress (14 further patients will be included).