Latest PUBLICATIONS

  • Executive resting-state network connectivity in migraine without aura.
    Publication Date: 01/10/2012, on Cephalalgia : an international journal of headache
    by Russo A, Tessitore A, Giordano A, Corbo D, Marcuccio L, De Stefano M, Salemi F, Conforti R, Esposito F, Tedeschi G
    DOI: 10.1177/0333102412457089

    Converging neuropsychological evidence suggests that in migraine executive functions (EF) may be affected during interictal periods.

  • N-methylated tryptamine derivatives in citrus genus plants: identification of N,N,N-trimethyltryptamine in bergamot.
    Publication Date: 19/09/2012, on Journal of agricultural and food chemistry
    by Servillo L, Giovane A, Balestrieri ML, Cautela D, Castaldo D
    DOI: 10.1021/jf302767e

    The occurrence of N-methylated tryptamine derivatives in bergamot plant (Citrus bergamia Risso et Poit) is reported for the first time. Interestingly, the most abundant of these substances is N,N,N-trimethyltryptamine, which has not been previously identified in any citrus plant. The N-methylated tryptamine derivatives were identified and quantitated in leaves, peel, juice, and seeds by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. N,N,N-Trimethyltryptamine was confirmed by MS(3) and comparison with the synthesized authentic standard. In addition, the study of the distribution of tryptophan, tryptamine, N-methyltryptamine, N,N-dimethyltryptamine, and N,N,N-trimethyltryptamine indicated that these compounds are differently expressed in the various tissues of the bergamot plant. Intriguingly, chemically synthesized N,N,N-trimethyltryptamine was reported to possess nicotine-like activity being a stimulant of parasympathetic ganglia by exerting its action on acetylcholine receptors. On this basis, the identification of N,N,N-trimethyltryptamine at a relatively high level in leaves suggests a possible role in a physiological mechanism of plant defense.

  • Involvement of autophagy in ovarian cancer: a working hypothesis.
    Publication Date: 13/09/2012, on Journal of ovarian research
    by Peracchio C, Alabiso O, Valente G, Isidoro C
    DOI: 10.1186/1757-2215-5-22

    Autophagy is a lysosomal-driven catabolic process that contributes to preserve cell and tissue homeostases through the regular elimination of damaged, aged and redundant self-constituents. In normal cells, autophagy protects from DNA mutation and carcinogenesis by preventive elimination of pro-oxidative mitochondria and protein aggregates. Mutations in oncogenes and oncosuppressor genes dysregulate autophagy. Up-regulated autophagy may confer chemo- and radio-resistance to cancer cells, and also a pro-survival advantage in cancer cells experiencing oxygen and nutrient shortage. This fact is the rationale for using autophagy inhibitors along with anti-neoplastic therapies. Yet, aberrant hyper-induction of autophagy can lead to cell death, and this phenomenon could also be exploited for cancer therapy. The actual level of autophagy in the cancer cell is greatly affected by vascularization, inflammation, and stromal cell infiltration. In addition, small non-coding microRNAs have recently emerged as important epigenetic modulators of autophagy. The present review focuses on the potential involvement of macroautophagy, and on its genetic and epigenetic regulation, in ovarian cancer pathogenesis and progression.

  • Recurrent hyperCKemia with normal muscle biopsy in a pediatric patient with neuromyelitis optica.
    Publication Date: 11/09/2012, on Neurology
    by Di Filippo M, Franciotta D, Massa R, Di Gregorio M, Zardini E, Gastaldi M, Terracciano C, Rastelli E, Gaetani L, Iannone A, Menduno P, Floridi P, Sarchielli P, Calabresi P
    DOI: 10.1212/WNL.0b013e3182698d39

  • Low concentrations of isothiocyanates protect mesenchymal stem cells from oxidative injuries, while high concentrations exacerbate DNA damage.
    Publication Date: 01/09/2012, on Apoptosis : an international journal on programmed cell death
    by Zanichelli F, Capasso S, Di Bernardo G, Cipollaro M, Pagnotta E, Cartenì M, Casale F, Iori R, Giordano A, Galderisi U
    DOI: 10.1007/s10495-012-0740-3

    Isothiocyanates (ITCs) are molecules naturally present in many cruciferous vegetables (broccoli, black radish, daikon radish, and cauliflowers). Several studies suggest that cruciferous vegetable consumption may reduce cancer risk and slow the aging process. To investigate the effect of ITCs on cellular DNA damage, we evaluated the effects of two different ITCs [sulforaphane (SFN) and raphasatin (RPS)] on the biology of human mesenchymal stem cells (MSCs), which, in addition to their ability to differentiate into mesenchymal tissues, contribute to the homeostatic maintenance of many organs. The choice of SFN and RPS relies on two considerations: they are among the most popular cruciferous vegetables in the diet of western and eastern countries, respectively, and their bioactive properties may differ since they possess specific molecular moiety. Our investigation evidenced that MSCs incubated with low doses of SFN and RPS show reduced in vitro oxidative stress. Moreover, these cells are protected from oxidative damages induced by hydrogen peroxide, while no protection was evident following treatment with the UV ray of a double strand DNA damaging drug, such as doxorubicin. High concentrations of both ITCs induced cytotoxic effects in MSC cultures and further increased DNA damage induced by peroxides. In summary, our study suggests that ITCs, at low doses, may contribute to slowing the aging process related to oxidative DNA damage. Moreover, in cancer treatment, low doses of ITCs may be used as an adjuvant to reduce chemotherapy-induced oxidative stress, while high doses may synergize with anticancer drugs to promote cell DNA damage.

  • Quantitative assessment of visual behavior in disorders of consciousness.
    Publication Date: 01/09/2012, on Journal of neurology
    by Trojano L, Moretta P, Loreto V, Cozzolino A, Santoro L, Estraneo A
    DOI: 10.1007/s00415-012-6435-4

    The study of eye behavior is of paramount importance in the differential diagnosis of disorders of consciousness (DoC). In spite of this, assessment of eye movement patterns in patients with vegetative state (VS) or minimally conscious state (MCS) only relies on clinical evaluation. In this study we aimed to provide a quantitative assessment of visual tracking behavior in response to moving stimuli in DoC patients. Nine VS patients and nine MCS patients were recruited in a Neurorehabilitation Unit for patients with chronic DoC; 11 matched healthy subjects were tested as the control group. All participants under went a quantitative evaluation of eye-tracking pattern by means of a computerized infrared eye-tracker system; stimuli were represented by a red circle or a small color picture slowly moving on a PC monitor. The proportion of on- or off-target fixations differed significantly between MCS and VS. Most importantly, the distribution of fixations on or off the target in all VS patients was at or below the chance level, whereas in the MCS group seven out of nine patients showed a proportion of on-target fixations significantly higher than the chance level. Fixation length did not differ among the three groups significantly. The present quantitative assessment of visual behaviour in a tracking task demonstrated that MCS and VS patients differ in the proportion of on-target fixations. These results could have important clinical implications since the quantitative analysis of visual behavior might provide additional elements in the differential diagnosis of DoC.

  • Paget's Disease. A Case Report.
    Publication Date: 01/09/2012, on The neuroradiology journal
    by Conforti R, Galasso R, Marrone V, Urciuoli L, Cirillo S
    DOI: 10.1177/197140091202500410

    Paget's disease (PD) is a common focal progressive osteometabolic disorder characterised by a disturbance in bone modelling and remodelling, because of an increase in osteoblastic and osteoclastic activity. It is a condition of unknown aetiology affecting approximately 3% of the population over 40 years of age and, approximately 10% of those over the age of 85 years. It is most common in Northern Europe and Australia and is rare in Asia and Africa. We describe the case of a 71-year-old man diagnosed with PD confined to the sacrum. After laboratory test, an imaging study with radiography, scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) was performed disclosing findings compatible with Paget's disease in middle pathologic phase. The diagnosis was confirmed at biopsy. The structural modification of the sacrum with spongiosa rarefaction, thickening of bone and intact bone cortical, confirmed by CT, are tipical of an intermediate phase of PD. This was also supported by signal MRI changes showing substitution of the red by the fat medulla, visualized by FS sequences. Once the treatment for the bone disease was established, the patient no longer complained of pain. Special attention should be paid to male and elderly patients with pain in the lumbar spine because of the potential risk cancer development (21). The radiologist must be attentive to the possible presentations and complications of PD, even in uncommon sites, trying whenever possible to correlate the radiological features with the patient's clinical symptoms.

  • Giant dilatations of virchow-robin spaces in the midbrain. MRI aspects and review of the literature.
    Publication Date: 01/09/2012, on The neuroradiology journal
    by Algin O, Conforti R, Saturnino PP, Ozmen E, Cirillo M, Di Costanzo A, De Cristofaro M, Rotondo M, Cirillo S
    DOI: 10.1177/197140091202500404

    Virchow-Robin spaces are lesions often seen in the brain parenchyma but their etiopathogenesis remains unsettled. Giant Virchow-Robin spaces placed in the midbrain are extremely rare. We describe three patients with a diagnosis of giant Virchow-Robin spaces in the midbrain, and their clinical and radiologic findings. We reviewed the literature in terms of the etiopathology, anatomic and radiologic appearance and differential diagnosis of the giant Virchow-Robin spaces. The diagno-stic role of the high Tesla magnetic resonance devices and new sequences techniques such as three dimensional isotropic acquisition and diffusion tensor imaging were also evaluated in this case series.

  • Serial T-SPOT.TB and quantiFERON-TB-Gold In-Tube assays to monitor response to antitubercular treatment in Italian children with active or latent tuberculosis infection.
    Publication Date: 01/09/2012, on The Pediatric infectious disease journal
    by Chiappini E, Bonsignori F, Mangone G, Galli L, Mazzantini R, Sollai S, Azzari C, de Martino M
    DOI: 10.1097/INF.0b013e31825d0d67

    We performed a prospective study to investigate T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-G-IT) dynamics during antitubercular treatment in active tuberculosis (TB) or latent TB. Eighteen children with latent TB and 26 with TB were enrolled. At 6 months of follow-up reversion rate was 5.88% (95% CI:0-13.79) for QFT-G-IT; 9.09% (95% CI:0.59-17.58) for T-SPOT.TB (P=0.921) in TB cases. Significant decline in quantitative response was observed exclusively in TB cases. Our results suggest that serial IGRA have limited use in children receiving antitubercular treatment.

  • Pain processing in patients with migraine: an event-related fMRI study during trigeminal nociceptive stimulation.
    Publication Date: 01/09/2012, on Journal of neurology
    by Russo A, Tessitore A, Esposito F, Marcuccio L, Giordano A, Conforti R, Truini A, Paccone A, d'Onofrio F, Tedeschi G
    DOI: 10.1007/s00415-012-6438-1

    We explored the functional pattern of the pain-processing network in patients with migraine, in the interictal periods, during trigeminal noxious stimulation. Contact heat evoked potential stimulation induced thermal pain and functional magnetic resonance imaging were used to measure whole-brain activation in 16 patients with episodic migraine without aura and 16 age- and gender-matched healthy controls in response to a severe (53°C) noxious, a moderate (51°C) noxious, and a control (41°C) stimulus applied to the maxillary skin. When comparing the fMRI activation over the entire brain, patients with migraine, with respect to healthy controls, showed a significantly greater activation in the perigenual part of anterior cingulate cortex at 51°C and less activation in the bilateral secondary somatosensory cortex at 53°C. A group-by-stimulus interaction analysis revealed a region in the pons showing a divergent response in patients and healthy controls. Correlation analyses demonstrated that the pons activation correlated with higher headache-related disability in patients. Our findings demonstrate increased antinociceptive activity in patients with migraine, which may represent a compensatory reorganization to modulate pain perception at the same intensity of healthy controls.

  • Subretinal Fibrosis in Stargardt's Disease with Fundus Flavimaculatus and ABCA4 Gene Mutation.
    Publication Date: 01/09/2012, on Case reports in ophthalmology
    by Rossi S, Testa F, Attanasio M, Orrico A, de Benedictis A, Corte MD, Simonelli F
    DOI: 10.1159/000345415

    To report on 4 patients affected by Stargardt's disease (STGD) with fundus flavimaculatus (FFM) and ABCA4 gene mutation associated with subretinal fibrosis.

  • Dopamine induces apoptosis in APPswe-expressing Neuro2A cells following Pepstatin-sensitive proteolysis of APP in acid compartments.
    Publication Date: 30/08/2012, on Brain research
    by Cagnin M, Ozzano M, Bellio N, Fiorentino I, Follo C, Isidoro C
    DOI: 10.1016/j.brainres.2012.06.025

    A pathological hallmark of Alzheimer's disease (AD) is the presence within neurons and the interneuronal space of aggregates of β-amyloid (Aβ) peptides that originate from an abnormal proteolytic processing of the amyloid precursor protein (APP). The aspartyl proteases that initiate this processing act in the Golgi and endosomal compartments. Here, we show that the neurotransmitter dopamine stimulates the rapid endocytosis and processing of APP and induces apoptosis in neuroblastoma Neuro2A cells over-expressing transgenic human APP (Swedish mutant). Apoptosis could be prevented by impairing Pepstatin-sensitive and acid-dependent proteolysis of APP within endosomal-lysosomal compartments. The γ-secretase inhibitor L685,458 and the α-secretase stimulator phorbol ester elicited protection from dopamine-induced proteolysis of APP and cell toxicity. Our data shed lights on the mechanistic link between dopamine excitotoxicity, processing of APP and neuronal cell death. Since AD often associates with parkinsonian symptoms, which is suggestive of dopaminergic neurodegeneration, the present data provide the rationale for the therapeutic use of lysosomal activity inhibitors such as chloroquine or Pepstatin A to alleviate the progression of AD leading to onset of parkinsonism.

  • A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease.
    Publication Date: 07/08/2012, on Neurology
    by Hamlin C, Puoti G, Berri S, Sting E, Harris C, Cohen M, Spear C, Bizzi A, Debanne SM, Rowland DY
    DOI: 10.1212/WNL.0b013e318263565f

    To compare the respective efficiency of CSF tau (quantitative) and CSF 14-3-3 protein (qualitative) in the diagnosis of prion disease.

  • Tedarenes A and B: structural and stereochemical analysis of two new strained cyclic diarylheptanoids from the marine sponge Tedania ignis.
    Publication Date: 03/08/2012, on The Journal of organic chemistry
    by Costantino V, Fattorusso E, Mangoni A, Perinu C, Teta R, Panza E, Ianaro A
    DOI: 10.1021/jo300295j

    Ring strain causes planar chirality in tedarenes A and B, two cyclic diarylheptanoids isolated from the marine sponge Tedania ignis. In both molecules, the chiral plane is an olefinic system, which is very rare among natural products. In tedarene A (1), interconversion is too fast to allow isolation of the enantiomeric atropisomers but still slow enough to cause coalescence of some (1)H and (13)C NMR signals at room temperature. In tedarene B (2), which also shows stable central and axial chirality, the two planar diastereomers are in slow equilibrium. Tedarene B is the smallest natural product with central, axial, and planar chirality in the same simple molecule. The identification of planar chirality as the difference between its conformational isomers allowed the use of theoretical prediction of the CD spectrum to determine the absolute configuration of the stereogenic carbon C-9 as well as of the biphenyl chiral axis.

  • Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients.
    Publication Date: 19/07/2012, on Biomedical engineering online
    by Melillo P, Pecchia L, Testa F, Rossi S, Bennett J, Simonelli F
    DOI: 10.1186/1475-925X-11-40

    Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA). In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA) involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration.