Characterisation of functional deficits induced by AAV overexpression of alpha-synuclein in rats.

Background: In the last decades different preclinical animal models of Parkinson's disease (PD) have been generated, aiming to mimic the progressive neuronal loss of midbrain dopaminergic (DA) cells as well as motor and non-motor impairment. Among all the available models, AAV-based models of human alpha-synuclein (h-aSYN) overexpression are promising tools for investigation of disease progression and therapeutic interventions. Objectives: The goal with this work was to characterise the impairment in motor and non-motor domains following nigrostriatal overexpression of h-aSYN and correlate the behavioural deficits with histological assessment of associated pathology. Methods: Intranigral injection of an AAV9 expressing h-aSYN was compared with untreated animals, 6-OHDA and AAV9 expressing either no transgene or GFP. The animals were assessed on a series of simple and complex behavioural tasks probing motor and non-motor domains. Post-mortem neuropathology was analysed using immunohistochemical methods. Results: Overexpression of h-aSYN led to progressive degeneration of DA neurons of the SN and axonal terminals in the striatum (STR). We observed extensive nigral and striatal pathology, resembling that of human PD brain, as well as the development of stable progressive deficit in simple motor tasks and in non-motor domains such as deficits in motivation and lateralised neglect. Conclusions: In the present work we characterized a rat model of PD that closely resembles human PD pathology at the histological and behavioural level. The correlation of cell loss with behavioural performance enables the selection of rats which can be used in neuroprotective or neurorestorative therapies.

Orbital dependent coherence temperature and optical anisotropy of V2O3 quasiparticles.

We report on an orbital and temperature dependent study of the onset of coherent quasiparticles in V2O3 single crystal. By using polarized infrared spectroscopy we demonstrate that the electronic coherence temperature is strongly orbital dependent, being about 400 K for [Formula: see text] orbitals and 500 K for the [Formula: see text]. This suggests that V2O3 low energy electrodynamics can be described in terms of two electron liquids differently renormalized by electronic correlations.

Fermi Surface of Metallic V_{2}O_{3} from Angle-Resolved Photoemission: Mid-level Filling of e_{g}

Using angle resolved photoemission spectroscopy, we report the first band dispersions and distinct features of the bulk Fermi surface (FS) in the paramagnetic metallic phase of the prototypical metal-insulator transition material V_{2}O_{3}. Along the c axis we observe both an electron pocket and a triangular holelike FS topology, showing that both V 3d a_{1g} and e_{g}^{π} states contribute to the FS. These results challenge the existing correlation-enhanced crystal field splitting theoretical explanation for the transition mechanism and pave the way for the solution of this mystery.

Infrared evidence of a Slater metal-insulator transition in NaOsO3.

The magnetically driven metal-insulator transition (MIT) was predicted by Slater in the fifties. Here a long-range antiferromagnetic (AF) order can open up a gap at the Brillouin electronic band boundary regardless of the Coulomb repulsion magnitude. However, while many low-dimensional organic conductors display evidence for an AF driven MIT, in three-dimensional (3D) systems the Slater MIT still remains elusive. We employ terahertz and infrared spectroscopy to investigate the MIT in the NaOsO3 3D antiferromagnet. From the optical conductivity analysis we find evidence for a continuous opening of the energy gap, whose temperature dependence can be well described in terms of a second order phase transition. The comparison between the experimental Drude spectral weight and the one calculated through Local Density Approximation (LDA) shows that electronic correlations play a limited role in the MIT. All the experimental evidence demonstrates that NaOsO3 is the first known 3D Slater insulator.

Effect of MN (III) tetrakis (4-benzoic acid) porphyrin by photodynamically generated free radicals on SODs keratinocytes.

Superoxide, a reactive form of oxygen, can be produced in vivo either in normal and under pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. Photodynamic therapies (PDT), widely adopted in Dermatology and Oncology, are known to generate reactive oxygen species (ROS) and may contribute to structural alterations and oxidatively generated modifications of cellular antioxidants. We hypothesized that over-production of free radicals would decrease the enzymatic activities of endogenous cellular antioxidants. To test this hypothesis, keratinocytes were treated with the photosensitizer Photofrin plus visible light to produce free radicals and CuZnSOD and MnSOD activities were measured. Photodynamic treatment of keratinocytes increases malonylaldehyde production, nitrotyrosine staining and superoxide production. The enzymatic activities of CuZnSOD and MnSOD were significantly decreased after Photofrin plus visible light treatment. Our results suggest that the main cellular antioxidant system can be inactivated by photodynamically generated ROS. Pretreatment of keratinocytes with free radicals scavenger such as Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) was able to restore the endogenous antioxidant system activities, inhibiting the MDA formation, nitrotyrosine staining and superoxide formation. Antioxidant therapy could therefore be a useful tool in protecting healthy epidermal cells against common side effects induced by antitumor targeted therapies.

Tetralogy of Fallot variant with pulmonary atresia (pseudotruncus arteriosus) in a case of maternal PKU syndrome.

The authors report on a child with a rare variant of the Tetralogy of Fallot with pulmonary atresia also known as Pseudotruncus arteriosus, who was born by a mother affected by classic phenylketonuria (PKU), diet free of phenylalanine until the age of seven years. According to the authors, this is the first example of such rare variant in an offspring of maternal PKU syndrome.

Bilateral congenital absence of internal carotid arteries in a woman with dementia. A case report.

Dysgenesis of THE internal carotid artery is considered a rare condition, present in about 0.01% of subjects. This anomaly is generally asymptomatic and often represents an incidental finding in radiological examinations of the head performed for other reasons. A 75-year-old woman with symptoms of dementia was admitted to our hospital. Computed tomography and magnetic resonance examinations were performed. They showed the absence of both internal carotid arteries and the congenital nature of this abnormality. The usefulness of CT and MRI examinations in patients with this vascular abnormality is discussed.

Molecular modelling and enzymatic studies of acetylcholinesterase and butyrylcholinesterase recognition with paraquat and related compounds.

The potent herbicide paraquat and three other analogues MPP+, MPDP+ and MPTP have a known toxicological profile linked to the ability to damage dopaminergic neurons. Other biological effects were recently addressed to this class of compounds, including the ability to interact with enzymatic targets involved in the Central Nervous System, such as the acetylcholinesterase (AChE) and the butyrylcholinesterase (BuChE). A combined molecular modelling and enzymatic study focusing onto their interaction against the AChE and BuChE is reported. The former study was performed by docking techniques using target known co-crystallographic models. The latter study was carried out by the widely adopted Ellman's method. In both studies the anti-Alzheimer FDA approved drug tacrine was used as reference inhibitor. Our results indicate that paraquat, MPTP, MPDP+ and MPP+ recognize both enzymatic cleft in a similar fashion compared to the reference inhibitor. A structure-activity correlation was found with the net charge of the ligands, indicating a major role of the electrostatic term in the recognition and inhibition of these compounds. Our data completed their enzymatic profile, added new information on the molecular mechanisms underlying their neurotoxicity useful for the rational design of new cholinesterase inhibitors.

Blink reflex abnormalities in children with Tourette syndrome.

Tourette syndrome (TS) is a common disorder which typically occurs during childhood or early adolescence. There is no definitive diagnostic test for TS. The objective of this study was to demonstrate whether neurophysiological abnormalities of the blink reflex can be observed in children with TS. We enrolled 15 children with TS, diagnosed according to DSM IV Diagnostic Criteria, and 15 controls. The blink reflex was elicited by stimulating the supraorbital nerve in order to measure the early response (R1), homolateral and contralateral R2 (late) responses, amplitude of R1 and duration of R2. The mean duration of R2 was significantly longer in TS patients than in the controls (P < 0.001, Student's t-test). An abnormal pattern of the blink reflex can be, even in childhood, an early neurophysiologic marker of TS, which is not related to the duration of TS or to the age of onset.

Progressive supranuclear palsy: a systematic review.

The progressive supranuclear palsy (PSP) is a rapidly progressing degenerative disease belonging to the family of tauophaties, characterized by the involvement of both cortical and subcortical structures. Although the pathogenesis of PSP is still uncertain, genetic, biochemical, and immunohistochemical studies have been performed and are reviewed here. Genetic factors, oxidative damage, neurotoxins, and environmental factors contribute to tau deposition in the cerebral areas involved in PSP. Symptoms originate from the ensuing dysfunction of dopaminergic, GABAergic, cholinergic, and noradrenergic pathways. Recent advances in neuroradiological and instrumental examinations facilitate the diagnosis and have gained new insights into the pathophysiology of PSP, although the primary cause of the disease is unknown and disease-modifying drugs are not yet available.

[Gilles de la Tourette's syndrome: a systematic review]. / Sindrome di Gilles de la Tourette: una review sistematica.

Gilles de la Tourette's syndrome is more frequent than once believed. This syndrome is a chronic disorder whose long term outcome is generally favourable, characterized by a fluctuating course. The etiopathogenesis of Gilles de la Tourette's syndrome has not been ascertained, although the frontal-subcortical neural pathways seem to be involved. This extrapyramidal syndrome is frequently associated with attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and behaviour problems. A correct diagnosis is the first step for a proper management of this disorder, which makes use of behavioural and pharmacological interventions.

Different clinical and evolutional patterns in late idiopathic and vascular parkinsonism.

OBJECTIVE: The aim of this study was to examine the clinical picture of Parkinson's disease (PD) and vascular parkinsonism (VP) in the elderly, in an attempt to differentiate the clinical history, symptoms, signs and response to therapy. MATERIAL AND METHODS: Thirty-two elderly patients with late onset PD and 45 with VP were enrolled and the clinical features of two groups were compared. All patients underwent brain MRI and were scored using the Unified Parkinson's Disease Rating Scales (UPDRS) -II, -III. RESULTS: Patients with PD had a younger age at onset and a longer duration of the disease as compared to patients with VP. Nearly all PD patients showed a good response to levodopa therapy, while only 29% of patients with VP were responsive to levodopa treatment. Vascular risk factors as well as postural tremor, gait disorders and pyramidal signs with lower body predominance, were more frequent in patients with VP. Ninety-three % of PD patients had normal MRI, whereas all patients with VP had cerebral vascular lesions. UPDRS-II, -III scores at baseline were higher in VP than in PD patients and their increases throughout the follow-up period were more marked in VP than in PD patients. CONCLUSIONS: Clinical history, symptoms, signs, response to therapy, and brain imaging help to differentiate PD and VP as two clinical entities with different clinical, prognostic and therapeutic implications, even if the coexistence of PD and a cerebral vascular disease in elderly patients is not infrequent and can make the diagnosis difficult.

Dementia with Lewy bodies: a review.

The dementia with Lewy bodies (DLB) is the second major type of senile, degenerative dementia, after the Alzheimer disease (AD). It is characterized by the presence of cytoplasmic inclusions of alpha-synuclein in the cerebral cortex and in the nuclei of the brain stem. DLB patients frequently have complex visual hallucinations, depressive symptoms, Parkinsonian manifestations and cognitive deficits, showing important associations with the Parkinson disease and the AD. The DLB should be differentiated from atypical Parkinsonisms, but the differential diagnosis often remains difficult and unsafe. Clinical and neuropathological findings, as well as neuroimaging are valuable tools in establishing specific diagnosis of DLB. Acetylcholinesterase inhibitors, dopamine-agonists, benzodiazepines of short or medium half-life, and antidepressants may be useful in the treatment of DLB, depending on the dominant symptoms of the given patients.

Efficacy and safety of fixed-dose oral sildenafil in the treatment of sexual dysfunction in depressed patients with idiopathic Parkinson's disease.

OBJECTIVE AND METHODS: The efficacy and safety of oral Sildenafil, a potent inhibitor of phosphodiesterase type 5, were evaluated in depressed men with idiopathic Parkinson's disease and erectile dysfunction. Thirty-three men were enrolled in a 4-month prospective, open-label, fixed-dose study, and received 50mg of Sildenafil in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of IIEF, a global efficacy question, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale-21 (HDRS-21). RESULTS: At the end of the study, improved erections were reported by 84.8% of patients. Sildenafil significantly increased patients' ability to achieve and maintain erections. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction and overall sexual satisfaction. BDI and HDRS scores improved from baseline to the end of the study. A clear improvement of depressive symptoms was observed in 75% of patients. Sildenafil was well tolerated in all the patients. CONCLUSIONS: Treatment with oral Sildenafil improves erectile function and, indirectly, depressive symptoms in patients with idiopathic Parkinson's disease stages 1-3, and is well tolerated.