fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study.

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.

Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients.

AIM: This observational study investigates the use of adjuvant trastuzumab (AT) in HER2-positive breast cancer patients in a real-life setting, focusing on relapse and discontinuation rates. PATIENTS & METHODS: Data on a group of HER2-positive patients collected from 13 oncology centers of northeast Italy were analyzed. RESULTS: In total, 1245 patients were analyzed. 13.1% of patients were excluded from AT because of comorbidities, age, tumor stage, refusal or other reasons; 8.2% of patients who received AT interrupted the therapy, mainly for toxicity. Overall the relapse rate was 10.9% in the AT-treated population versus 22.6% in nontreated patients (follow-up: 37.4 and 62.1 months, respectively). Disease-free survival (DFS) was lower in AT-relapsed patients than in not-relapsed. Statistical analysis showed a correlation between DFS and estrogen receptor status in AT-treated patients. CONCLUSION: Relapse rates are lower in clinical setting compared to clinical trials. Overall, AT is effective in HER2-positive early-stage breast cancer patients.

Expression of two maize putative nitrate transporters in response to nitrate and sugar availability.

A full-length cDNA encoding a putative high-affinity nitrate transporter (ZmNrt2.2) from maize was isolated and characterised, together with another previously identified transporter (ZmNrt2.1), in terms of phylogenesis, protein structure prediction and regulation of transcript accumulation in response to nitrate and sugar availability. The expression of both genes was evaluated by quantitative and semi-quantitative RT-PCR in response to nitrate and sugar supply and the in planta localisation of mRNA was studied by in situ hybridisation. Data obtained suggested similar genetic evolution and identical transmembrane structure prediction between the two deduced proteins, and differences in both regulation of their expression and mRNA localisation in response to nitrate, leading us to hypothesise a principal role for ZmNRT2.1 in the influx activity and the major involvement of ZmNRT2.2 in the xylem loading process. Our data suggest opposing sugar regulation by ZmNrt2.1 and ZmNrt2.2 transcription in the presence or absence of nitrate and the existence of both hexokinase-dependent and hexokinase-independent transduction mechanisms for the regulation of ZmNrt2.1 and ZmNrt2.2 expression by sugars.

Chromate differentially affects the expression of a high-affinity sulfate transporter and isoforms of components of the sulfate assimilatory pathway in Zea mays (L.).

In this study the chromate accumulation and tolerance were investigated in ZEA MAYS L. in relation to sulfur availability since sulfate may interact with chromate for transport into the cells. Chromate inhibited sulfate uptake when supplied to plants for a short-term period, whereas phosphate uptake remained unchanged. Sulfate absorption was also reduced in S-starved (-S) and S-supplied (+S) plants treated for 2 d with 0.2 mM chromate and the concomitant repression of the root high-affinity sulfate root transporter ZMST1;1 transcript accumulation was observed. Conversely, the plasma membrane H (+)-ATPase MHA2 was unaffected by chromate in +S plants, allowing to exclude a general effect of chromate on the active membrane transport. As observed for sulfate uptake, chromate uptake was enhanced in -S condition and decreased in both +S and -S plants after 2 d of Cr treatment. Chromate reduced the concentration of sulfur and sulfate in +S plants to the basal level of -S plants, and maximum chromium accumulation was recorded in S-deprived plants. Analysis of transcript abundance of genes involved in sulfate assimilation revealed differential regulation by chromate, which was only partly related to sulfur availability and to the levels of thiols. This work shows for the first time that chromate specifically represses sulfate uptake, and such repression occurs without the implication of the candidate regulatory metabolites of the sulfate transport system in plants.

Oscillatory magnetic anisotropy in one-dimensional atomic wires.

One-dimensional Co atomic wires grown on Pt(997) have been investigated by x-ray magnetic circular dichroism. Strong changes of the magnetic properties are observed as the system evolves from 1D- to 2D-like. The easy axis of magnetization, the magnetic anisotropy energy, and the coercive field oscillate as a function of the transverse width of the wires, in agreement with theoretical predictions for 1D metal systems.

A multimode analysis of the gas-phase photoelectron spectra in oligoacenes.

We present a multimode vibrational analysis of the gas-phase ultraviolet photoelectron spectra of the first ionization in anthracene, tetracene, and pentacene, using electron-vibration constants computed at the density functional theory level. The first ionization of each molecule exhibits a high-frequency vibronic structure; it is shown that this regularly spaced feature is actually the consequence of the collective action of several vibrational modes rather than the result of the interaction with a single mode. We interpret this feature in terms of the missing mode effect. We also discuss the vibronic coupling constants and relaxation energies obtained from the fit of the photoelectron spectra with the linear vibronic model.

[Surgical therapy of Crohn's disease: observations on 63 patients]. / La terapia chirurgica della malattia di Crohn. Considerazioni su una casistica di 63 osservazioni.

AIM: The purpose of our retrospective study is to evaluate the correct indications for the surgical therapy of Crohn's disease. METHODS: Our case series consists of 63 patients admitted to our Surgery Department from January 1, 1973 to December 2002 with a diagnosis of Crohn's disease. Of the 56 operated patients, 43 patients were followed-up. For an objective evaluation of the Crohn's disease activity, the Crohn's Disease Activity Index (CDAI) was used. Surgical treatment has been carried out in 56 cases: in 29 cases of intestinal occlusion a minimal gut resection was performed; in the 26 cases of perforation a suture of the perforation was preferred, with a drainage of the peritoneal cavity and a toilette of abscess when it was present, and in 1 case an ileocolic resection was performed. RESULTS: Only 1 case showed a CDAI score >150 (153.63). This shows that in all the other cases the surgical and medical treatment has led to a satisfactory control of the disease. A relapse has been observed in 17 patients after an average period of 5 years without showing signs of disease. CONCLUSION: It is suggested that Crohn's disease therapy should be mainly of a medical nature and surgical treatment should be reserved for complicated cases.

Charge-transfer transitions in triarylamine mixed-valence systems: a joint density functional theory and vibronic coupling study.

A theoretical model is developed to describe the intramolecular transfer in organic mixed-valence systems. It is applied to rationalize the intervalence charge-transfer transitions in triarylamine mixed-valence compounds. The electronic coupling parameter is evaluated at the density functional theory (DFT) and time-dependent density functional theory (TD-DFT) levels. The shapes of the charge-transfer absorption bands are analyzed in the framework of a dynamic vibronic model. The influence on the optical properties of diagonal and nondiagonal vibronic couplings is discussed. Our results are compared to recent experimental data.

Finite temperature magnetism in Gd: evidence against a Stoner behavior.

The temperature dependence of the rare-earth valence bands has been regarded as a realization of the Stoner behavior. The exchange splitting of the electronic states appears to scale as the magnetic order parameter for T

Ferromagnetism in one-dimensional monatomic metal chains.

Two-dimensional systems, such as ultrathin epitaxial films and superlattices, display magnetic properties distinct from bulk materials. A challenging aim of current research in magnetism is to explore structures of still lower dimensionality. As the dimensionality of a physical system is reduced, magnetic ordering tends to decrease as fluctuations become relatively more important. Spin lattice models predict that an infinite one-dimensional linear chain with short-range magnetic interactions spontaneously breaks up into segments with different orientation of the magnetization, thereby prohibiting long-range ferromagnetic order at a finite temperature. These models, however, do not take into account kinetic barriers to reaching equilibrium or interactions with the substrates that support the one-dimensional nanostructures. Here we demonstrate the existence of both short- and long-range ferromagnetic order for one-dimensional monatomic chains of Co constructed on a Pt substrate. We find evidence that the monatomic chains consist of thermally fluctuating segments of ferromagnetically coupled atoms which, below a threshold temperature, evolve into a ferromagnetic long-range-ordered state owing to the presence of anisotropy barriers. The Co chains are characterized by large localized orbital moments and correspondingly large magnetic anisotropy energies compared to two-dimensional films and bulk Co.

Hole- and electron-vibrational couplings in oligoacene crystals: intramolecular contributions.

The hole-vibrational coupling is reported for anthracene, tetracene, and pentacene on the basis of a joint experimental and theoretical study of ionization spectra using high-resolution gas-phase photoelectron spectroscopy and first-principles correlated quantum-mechanical calculations. The hole-vibrational coupling is found to be significantly smaller than the electron-vibrational coupling in the case of these oligomers; however, both quantities are predicted to converge to the same value when increasing the chain length.

Electronic band structure of Gd: a consistent description.

The dispersion of the Gd (5d6s)-valence bands has been investigated by means of spin- and angle-resolved photoemission. The spin analysis of various spectral features shows that their weak dispersion and unusual broadening is due to the photoelectron lifetime rather than to correlation induced band narrowing as previously proposed. These results resolve a long-standing discrepancy between theoretical and experimental descriptions of the rare earth band structure.

Antiviral and antiproliferative activity in vitro of some new benzimidazole derivatives.

The antiviral and antiproliferative activity of new compounds having n-benzenesulphony 1-2 (2 or 3-pyridylethyl) benzimidazole as a base structure were studied in vitro. Their antitumour activity against human chronic myeloid leukaemia cells was evaluated and compared with that of equimolar doses of daunorubicin. Only compound 7a, with the presence of both the pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro-group in the benzene ring, displays a selective antiproliferative effect against certain leukaemia cells and a good antiviral activity especially towards the Coxsackie B5 virus. However, it should be noted that, in the case of hydroxybenzyl-benzimidazole, resistance also builds up to compound 7a, the Coxsackie B5 virus developing resistance to it after about ten runs. Cytotoxicity tests show that many of these substances are well tolerated by the VERO cells. The mechanism of action is still unclear.

Cytotoxicity and probable mechanism of action of sulphimidazole.

Sulphimidazole (1-methyl-2((4-aminophenyl)-sulphonyl)-amino-5-nitroimidazole) is a new compound in which a p-aminobenzenesulphonamide radical has been attached at position 2 of the 5-nitroimidazole ring. It possesses a useful spectrum of activity in vitro against various anaerobic microorganisms and its action against aerobic and facultative bacteria is synergically enhanced in association with trimethoprim. In the present study, we determined the cytotoxicity in vitro of sulphimidazole and trimethoprim, both alone and in combination, and analysed the viability of Vero cells and the protein content of their cell lysate in the presence of increasing concentrations of these drugs. Also, in order to verify the hypothesis that the action of sulphimidazole against aerobic and facultative bacteria is mediated by the sulphonamide component of the molecule, while that against anaerobic bacteria depends on the action of the nitro group of the 5-nitroimidazole ring, we studied the mechanism of action of the new compound both indirectly, by means of microbiological techniques, and directly, by determining its oxidoreduction potential with respect to that of metronidazole. The results show that sulphimidazole is only slightly toxic in vitro for Vero cells, either alone or in association with trimethoprim, and that the combination of the two functional groups in a single molecule not only maintains its structure-activity relationship intact but also broadens its antibacterial spectrum.

Synthesis and antiproliferative activity of some benzimidazole-4,7-dione derivatives.

A series of benzimidazole-4,7-diones bearing at the 2-position the thiomethyl group or the 2-pyridyl moiety has been synthesized and tested in vitro on three tumor cell lines. Two of them show a very good antiproliferative effect. Compounds 1 and 2d are more active or equiactive, respectively, than MMC against human lymphoblastic leukemia. Both compounds exhibit high activity on human non-Hodgkin lymphoma. Compound 1 is non toxic at all the concentrations used in the antiproliferative assay and 2d is toxic only at high concentration.

Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: an experimental in vivo study.

The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.

Synthesis, antiviral and antiproliferative activity of some N-benzenesulphonyl-2(2- or 3-pyridylethyl)-benzimidazoles.

Some N-benzenesulphonyl-2(2- or 3-pyridylethyl)-benzimidazoles were synthesized and tested in vitro for antiproliferative and antiviral activity. Only one compound displayed a degree of antiproliferative activity against chronic myeloid leukaemia cells. However, a number of them exerted an antiviral effect at micromolar concentrations. The antiproliferative activity and the maximum potency of antiviral activity correlate with the presence of both the 2-pyridyl moiety bound at the ethylenic bridge in C-2 of benzimidazole and the nitro group in the benzene ring.

Synthesis and antiproliferative activity of some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]pyridines.

Some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]-pyridines were synthesized and tested in vitro for antiviral and antiproliferative activity. None of the compounds had antiviral properties. However, three of them inhibited the proliferation of leukaemia and lymphoma cell lines at micromolar concentrations. The maximum potency of antiproliferative activity is correlated with the presence of an ethylenic spacer between the two heterocycles.

In-vitro studies of two 5-nitroimidazole derivatives.

This paper reports the findings obtained using two new compounds belonging to the 5-nitroimidazole family: sulphuridazole (V1) and sulphonidazole (V2). We first assessed their antimicrobial activity on Clostridia spp. and then extended the study to Gram-positive and Gram-negative aerobic microorganisms and to Candida albicans. Their MICs were compared with those of metronidazole. The findings show that the antibacterial and antimycotic activity of sulphonidazole is greater than that of sulphuridazole, while metronidazole is not active against any aerobic organism. It also emerges that the NO2 group is indispensable for all the microorganisms assayed and that sulphuridazole and sulphonidazole are the first two 5-nitroimidazoles active against C. albicans. The redox potentials of the 5-nitroimidozoles studied suggest that their action mechanism is mainly based on redox processes.

Role of chemotherapeutic antagonism in opportunistic infections.

The most widely-known anti-tumor drugs often induce marked immunosuppression which can give rise to one or more sepses. Anti-infection measures immediately applied can sometimes prove largely ineffective or even useless, the patient dying not as a result of the spread of the tumour but as a direct consequence of opportunistic infection. We postulate that antagonism between anti-tumour and antimicrobial drugs may also play an important part in this. By way of illustration of this hypothesis, we have studied the action of a number of known inhibitors of peptidoglycan synthesis and of DNA-gyrases on certain strains of Gram-positive and Gram-negative microorganisms cultured in medium containing various concentrations of some of the best-known anti-tumour antimetabolites. The experimental data show that antimicrobial and anti-tumour drugs can sometimes induce synergic or indifferent chemotherapeutic interactions with many bacteria, while in others the effect is antagonistic. In practice, the action of the drugs could lead to bacterial selectivity, which, in conjunction with immunosuppression and the presence of resistant strains, could favour the evolution of opportunistic infection.