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Purpose: : Several studies have shown that patients with Alzheimer’s Disease (AD) have a significantly increased rate of glaucoma occurrence. The purpose of the study was to evaluate the frequency of glaucoma and changes of the optic... more
Purpose: : Several studies have shown that patients with Alzheimer’s Disease (AD) have a significantly increased rate of glaucoma occurrence. The purpose of the study was to evaluate the frequency of glaucoma and changes of the optic nerve head (ONH) morphology and/or retinal nerve fiber layer (RNFL) thickness in patients with AD. Methods: : 94 eyes of AD subjects and 127 eyes from age-matched controls underwent a complete eye examination including measurements of IOP, central corneal thickness and visual field testing using a Matrix FDT. ONH and RNFL assessment was performed both by slit lamp biomicroscopy and HRT III examination. The diagnosis of glaucoma was based on the presence of at least two of the following criteria: visual field defects characteristic of or compatible with glaucoma, specific ONH alterations and/or changes of HRT parameters. Results: : The Glaucoma Probability Score and Moorfields Regression Analysis (Mann Whitney U test: 0,004 and 0,001, respectively) and HRT3 stereometric parameters Rim Vol, RNFL thickness (ANOVA Tests of Between-Subjects Effects: 0,039 and 0,001, respectively) resulted significantly different along with the Matrix parameters MD (ANOVA: 0,001), PSD and GHT (Mann Whitney U test: 0,001 and 0,001 respectively) in patients with AD compared to the controls. The IOP mean value resulted to be significantly reduced (ANOVA: 0,001) in AD compared to controls. The frequency of glaucoma in AD patients (25,5 %) was significantly higher than in control group (5,5%) (p= 0.001). Conclusions: : The study confirmed that patients with AD have a higher frequency of glaucoma in the absence of elevated IOP levels. HRT III seems to be an useful tool in detecting ONH and RNFL changes in AD patients.
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We have studied Mongolian gerbils using somatosensory evoked potentials (SEP) recordings before, during and after an ischemic event. In six experimental animals, cerebral ischemia was reproduced by clamping both carotid arteries for ten... more
We have studied Mongolian gerbils using somatosensory evoked potentials (SEP) recordings before, during and after an ischemic event. In six experimental animals, cerebral ischemia was reproduced by clamping both carotid arteries for ten minutes. Two recordings were made during this period at 4' and 8'. An additional four recordings were made after removal of the clamp at 4', 8', 12' and 20'. Four animals were utilized as a control group, and were subjected to the identical experimental protocol, with the exclusion of carotid artery clamping. During ischemia we observed an evident alteration of the SEP recordings in the experimental animals, and a more or less rapid recovery during the post-ischemic period. This experimental model may be useful for the monitoring and the evaluation of the evolution of cerebro-vascular damage during the post-ischemic period.
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Dear Sirs, Although the origin of MS remains elusive, several studies have focused on different genetic-environmental factors; in particular, the role of Epstein–Barr Virus (EBV) infection and virus-triggered immunopathology have been... more
Dear Sirs, Although the origin of MS remains elusive, several studies have focused on different genetic-environmental factors; in particular, the role of Epstein–Barr Virus (EBV) infection and virus-triggered immunopathology have been investigated.1–2 We report on a 64-year-old male presenting with fever, lethargy, stiff neck, left-trigeminal and right-facial nerves deficit, astasia, sensory loss in lower limbs, hypotonic and areflexic paraparesis. CSF analysis showed lymphocytic and mononuclear pleocytosis, amplifiable EBVDNA and EBV IgM and IgG. Brain MRI was unremarkable; spinal MRI showed a diffuse T2-weighted high-signal intensity (T2HSI) along the thoracic cord with gadolinium enhancement, and lumbosacral impingement of nerve roots and meninges. The patient achieved a full recovery after intravenous (i.v.) therapy with acyclovir 10 mg/kg t.i.d. and methylprednisolone 1000 mg/day. Combined clinical, CSF and MRI findings led to the diagnosis of encephalomyelomeningoradiculitis related to EBV infection. After a long period of total well-being, the patient presented two acute episodes of lower limbs sensory-motor deficit and severe sphinteric retention. The episodes were separated by a considerable time and each was followed by almost complete recovery. Neurological examination showed in both episodes brisk tendon reflexes in the lower limbs, bilateral Babinski sign and clonus in Achilles tendon reflexes. On both occasions normal cell count and mild increment of protein, lactate and IgG were detected in the CSF, but intrathecal synthesis of oligoclonal bands (OCBs) was unexpectedly evident at the immunoelectrofocusing. Virology from CSF and serum, as vasculitic and rheumatological screens, was negative. Brain and spinal MRI documented the progressive increment in size and number of T2HSI lesions, not evident previously. Somatosensory and visual evoked potentials (SEPs; VEPs) showed bilateral delay of the P40, N20 and P100 waves. In both episodes, a five-day treatment with i.v. methylprednisolone 1000 mg/day produced a full recovery, except for a residual numbness in the feet and sphinteric retention. Therefore, episodes were notably associated to: i) neuraxis-MRI documenting the progressive dissemination in time and space of the white matter lesions; ii) CSF intrathecal synthesis of OCBs; iii) altered evoked potentials; iv) response to i.v. corticosteroids. On this evidence the diagnosis of a demyelinating process occurring after an EBV neuraxis infection was postulated. MS aetiology is still unknown, but one of the most interesting conjectures is that MS may be primed and perpetuated by a neurotropic agent, possibly a virus, in genetically susceptible subjects, suggesting that a virus may initiate or trigger immunopathological demyelinating processes.1 Different neurotropic viruses have been variously invoked as the possible cause of MS and EBV is considered the outstanding candidate.2 In fact, there is ample documentation that a history of symptomatic primary EBV infection increases the risk of developing MS; moreover, it has been recently hypothesized that EBV can promote inflammatory processes by activating innate immune responses, for example IFNα production,3 although these data are still debated.4 The present case documents a clear relationship between an EBV-CNS infection and the subsequent development of a CNS demyelinating process, probably due to an immunological cross-reaction, showing clinical and paraclinical features in agreement with the McDonald criteria for MS diagnosis.5 Hence, we propose that EBV should be considered as playing a possible crucial role as a trigger in the pathogenesis of demyelinating processes.
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Here we investigated the effect of the rivastigmine patch alone on depression in 50 mild... more
Here we investigated the effect of the rivastigmine patch alone on depression in 50 mild Alzheimer's disease (AD) patients with comorbid major depressive episode (MDE). First diagnosis acetyl-cholinesterase inhibitor and psychoactive drug-free outpatients (n=50) were recruited in memory clinics and reassessed after 3 and 6 months. Global cognitive functioning, depressive symptoms and MDE frequency were evaluated with the Mini Mental State Examination, the CERAD Dysphoria scale and the modified DSM-IV criteria for MDE in AD. MDE frequency reduced significantly from the first diagnostic visit (100%) to the 6-month follow-up (62%). We also found a significant reduction in CERAD Dysphoria scores that decreased from 6.2±3.9 mean±standard deviation to 4.9±4.5 at the 6-month follow-up. In AD patients with MDE rivastigmine alone can have a positive impact on depressive phenomena. Thus, future controlled study are justified to definitively verify if rivastigmine alone may improve depression in AD.
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Oxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the... more
Oxcarbazepine (OCBZ) is the keto-analogue of carbamazepine (CBZ). In humans, OCBZ is rapidly and almost completely metabolized to 10, 11-dihydro-10-hydroxy-CBZ (GP 47779), the main metabolite responsible for the drug's antiepileptic activity. The corticostriatal pathway is involved in the propagation of epileptic discharges. We characterized the electrophysiological effects of GP 47779 on striatal neurons by making intracellular recordings from corticostriatal slices. GP 47779 (3-100 microM) produced a dose-dependent inhibition of glutamatergic excitatory postsynaptic potentials (EPSPs). This effect was not coupled either with changes of the membrane potential of these cells or with alterations of their postsynaptic sensitivity to excitatory amino acids (EAA) suggesting a presynaptic site of action. GP 47779 reduced the current-evoked firing discharge only at concentrations > 100 microM. GP 47779 did not affect the presynaptic inhibitory action of adenosine, showing that presynaptic adenosine receptors were not implicated in the GP 47779-mediated reduction of corticostriatal EPSPs. Our data indicate that GP 47779 apparently acts directly on corticostriatal terminals to reduce the release of EAA, probably by inhibiting high-voltage-activated (HVA) calcium (Ca2+) currents (described in the accompanying article). The inhibitory action of GP 47779 on corticostriatal transmission may contribute to the antiepileptic effects of this drug.
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To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. In a group... more
To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment. Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics. These data demonstrate a reversible Helicobacter pylori (HP)-induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics.
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OBJECTIVE: To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations.... more
OBJECTIVE: To investigate if Helicobacter pylori (HP) eradication could make an effective and long-lasting improvement in the pharmacokinetic and clinical response to l-dopa in patients with Parkinson disease (PD) and motor fluctuations. METHODS: In a group of 34 HP-infected, motor-fluctuating patients with PD, the short-term (1-week) and long-term (3-month) beneficial effect of HP eradication (n = 17) was investigated in a double-blind fashion in comparison with a generic antioxidant treatment (n = 17), by means of pharmacokinetic, clinical, and gastrointestinal assessments. Results were compared with placebo treatment. RESULTS: Differently from the antioxidant-treated patients, the HP-eradicated patients showed a significant increase of l-dopa absorption, which was coupled with a significant improvement of clinical disability and with a prolonged "on-time" duration, whereas gastritis/duodenitis scores significantly decreased in line with a better l-dopa pharmacokinetics. CONCLUSIONS: These data demonstrate a reversible Helicobacter pylori (HP)-induced interference with l-dopa clinical response related to the impaired drug absorption, probably due to active gastroduodenitis. Therefore, the authors suggest that HP eradication may improve the clinical status of infected patients with Parkinson disease and motor fluctuations by modifying l-dopa pharmacokinetics
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CHAPTER 17 Manganese Toxicity: A Critical Reappraisal Patrizia Vernole, Maria Morello, Giuseppe Sancesario, Alessandro Martorana, Giorgio Bernard!, Antonella Canini, Palma Mattioli ABSTRACT Manganese is ... 1991; Jouve et al., 1975; Kimes... more
CHAPTER 17 Manganese Toxicity: A Critical Reappraisal Patrizia Vernole, Maria Morello, Giuseppe Sancesario, Alessandro Martorana, Giorgio Bernard!, Antonella Canini, Palma Mattioli ABSTRACT Manganese is ... 1991; Jouve et al., 1975; Kimes and Morris, 1973; Mullen et al ...
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Twenty-six metals and the oxidative status in 71 patients affected by Parkinson's disease and 44 healthy individuals were compared in order to identify potential biomarkers of the disease. In the patients, the following significant... more
Twenty-six metals and the oxidative status in 71 patients affected by Parkinson's disease and 44 healthy individuals were compared in order to identify potential biomarkers of the disease. In the patients, the following significant imbalances were found (p < or = 0.05): i) in serum, an increment of Ca, Mg, Ni, Si and V, and a decrement of Cd, Co, Fe, Li, Sn, Zn and Zr; ii) in blood, raised levels of Co, Li, Ni and Si and decreased of Al, Be, Ca, Cd, Fe, Mg, Mo, Sn, Zn and Zr; iii) increased formation of oxidant species and lowered anti-oxidant capacity (p < or = 0.001 for both). Barium, Bi, Cr, Cu, Hg, Mn, Pb, Sb, Sr, Tl and W did not change with the disease. The best discriminating variables between patients and controls were Cd, Co, Fe, Ni and Si in serum (91.2% of cases correctly classified), and Al, Cd, Co, Fe, Mo and Si in blood (98.2% of cases properly classified).
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In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a cost-effective and easy to use sensing tool for customized administration of drugs in Alzheimer's disease. Among several drugs,... more
In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a cost-effective and easy to use sensing tool for customized administration of drugs in Alzheimer's disease. Among several drugs, we designed the device for evaluating the efficacy of compounds (e.g. physostigmine, rivastigmine, donepezil) which are able to inhibit in a reversible way the cholinesterase enzyme. Because cholinesterase activity is peculiar to each patient, the administration of customized amount of the drug can improve the treatment efficacy and the quality of patient life, avoiding side effects due to the overdosage. In detail, we exploited Vivid™ Plasma Separation membrane to threat the whole blood sample, filter paper to load the reagents needed for the measurement, and office paper to print electrodes able to measure the butyrylcholinesterase activity, delivering a reagent free analytical tool. The calibration curve of butyrylcholinesterase obtained in blood sample provided linearity between 2 and 12 U/mL, with sensitivity of 0.050 ± 0.004 μA mL/U. The physostigmine, rivastigmine, and donepezil inhibition activities toward the butyrylcholinesterase enzyme were also measured in blood sample with linearity up to respectively 0.5 μM, 25 μM, 30 μM, and detection limits of 0.009 μM, 0.4 μM, 0.3 μM. These results demonstrate the capability of paper-based origami sensors as point of care devices to customize the drug administration in Alzheimer's disease.
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Involvement of metals in the risk of developing Parkinson&amp;amp;#39;s disease (PD) has been suggested. In the present study, concentration of metals in cerebrospinal fluid (CSF), blood, serum, urine and hair of 91 PD patients and 18... more
Involvement of metals in the risk of developing Parkinson&amp;amp;#39;s disease (PD) has been suggested. In the present study, concentration of metals in cerebrospinal fluid (CSF), blood, serum, urine and hair of 91 PD patients and 18 controls were compared. Blood and hair were microwave digested, while CSF, serum and urine were water-diluted. Elements quantification was achieved by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field Inductively Coupled Plasma Mass Spectrometry. Some metal imbalances in PD were observed: i), in CSF, lower Fe and Si; ii), in blood, higher Ca, Cu, Fe, Mg and Zn; iii), in serum, lower Al and Cu; iv), in urine, lower Al and Mn, higher Ca and Fe; and v), in hair, lower Fe. The ROC analysis suggested that blood Ca, Fe, Mg and Zn were the best discriminators between PD and controls. In addition, hair Ca and Mg were at least 1.5 times higher in females than in males of patients and controls. A decrement with age of patients in hair and urine Ca and, with less extent, in urine Si was observed. Magnesium concentration in CSF decreased with the duration and severity of the disease. Elements were not influenced by the type of antiparkinsonian therapy. Variation in elements with the disease do not exclude their involvement in the neurodegeneration of PD.
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Unilateral 6-hydroxydopamine-induced lesions of the substantia nigra have been used as an experimental model for Parkinson&#39;s disease. Although the biochemical and the behavioural effects of striatal denervation have been widely... more
Unilateral 6-hydroxydopamine-induced lesions of the substantia nigra have been used as an experimental model for Parkinson&#39;s disease. Although the biochemical and the behavioural effects of striatal denervation have been widely characterized, the physiological and pharmacological changes caused by dopamine depletion at the cellular level are still unknown. We studied the electrical activity of single rat striatal neurons recorded intracellularly in vitro from a brain slice preparation. Recordings were obtained at different periods after the denervation (4, 6, 8 months). In dopamine-denervated slices, unlike naive slices, most of the neurons showed spontaneous depolarizing postsynaptic potentials. The percentage of cells showing spontaneous depolarizing postsynaptic potentials was maximal 4 months after the denervation. In most of the dopamine-denervated neurons (60%) spontaneous depolarizing postsynaptic potentials were reversibly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), an antagonist of non-N-methyl-D-aspartate glutamate receptors. In some neurons, however, the amplitude of spontaneous depolarizing postsynaptic potentials was reduced by bicuculline (30 microM) suggesting that they were mediated by the release of endogenous gamma-aminobutyric acid (GABA). Intrinsic membrane properties (membrane potential, input resistance and firing pattern) and postsynaptic responses to different agonists of excitatory amino acid receptors were not altered in neurons recorded from dopamine-depleted slices. In dopamine-depleted slices, unlike in naive slices, LY 171555 (0.1-10 microM), a D2 dopamine receptor agonist, reduced the frequency and the amplitude of CNQX-sensitive spontaneous depolarizing postsynaptic potentials and reduced the amplitude of glutamate-mediated synaptic potentials evoked by cortical stimulation. LY 171555 did not affect the membrane responses to exogenous glutamate. SKF 38393 (3 microM), a D1 dopamine receptor agonist, decreased postsynaptic excitability of striatal neurons recorded from naive animals. On the contrary, this agonist was ineffective in most of the cells obtained from dopamine-depleted slices. These results suggest that dopamine-denervation augments neuronal excitability in the striatum. Abnormal excitability of striatal neurons is not caused by changes of the intrinsic membrane properties of these cells, but is the result of increased glutamatergic cortical inputs to the striatum. Dopamine-denervation also alters the physiological responses to dopamine receptor stimulation. Nigral lesions induce supersensitivity of D2 dopamine receptors controlling the release of glutamate and reduce the inhibitory influence of D1 receptors at postsynaptic level. These functional changes of the striatal neurons may alter the output signals from the striatum to the other structures of the basal ganglia and then produce most of the physiopathological changes observed in Parkinson&#39;s disease.
Research Interests: Chemistry, Electrophysiology, Medicine, Dopamine, Brain, and 14 moreAnimals, Male, Substantia nigra, Quinpirole, Denervation, Rats, Stimulation, Wistar Rats, Tetrodotoxin, Action Potentials, Nerve Conduction Velocity, Corpus striatum, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Neuroscience, Cognitive Science, Motor Learning, Long Term Potentiation, Biology, and 15 moreMedicine, Neurodegenerative Diseases, Dopamine, Animals, Neuronal Plasticity, Central Nervous System, Animal Model, Acetylcholine, Neurons, Long Term Depression, Basal ganglia, Membrane Potential, High Sensitivity, cyclic GMP, and Nerve degeneration
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The distribution of 3H-spiroperidol binding sites within rabbit superior mesenteric artery was studied in normal as well as 6-hydroxydopamine (6-OHDA) sympathectomized animals using a histoautoradiographic technique. The labelled drug was... more
The distribution of 3H-spiroperidol binding sites within rabbit superior mesenteric artery was studied in normal as well as 6-hydroxydopamine (6-OHDA) sympathectomized animals using a histoautoradiographic technique. The labelled drug was located in the three layers of the artery (adventitia, media and intima), with the greater density in the media. In the adventitia the radiolabelled drug was located at the level
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Frailty is an evolving concept that is generally defined in biomedical or psychosocial terms. It is not necessarily related to a specific single disease process. Passing by the theories of Selye (1936) on the exhaustion of the General... more
Frailty is an evolving concept that is generally defined in biomedical or psychosocial terms. It is not necessarily related to a specific single disease process. Passing by the theories of Selye (1936) on the exhaustion of the General Adaptation Syndrome,until reaching to the studies of Fried (2001) who, firstly, proposed diagnostic criteria for frailty, in this paper are explored different ways to understand this concept, until endeavour to give a possible modern view. The definition of a frailty syndrome characterized by a multi-system reduction in ?reserve capacity? remains widely accepted.
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Research Interests: Endocrinology, Positron Emission Tomography, Medicine, Cerebrospinal Fluid, Brain, and 13 moreHumans, Internal Medicine, Glucose, Default Mode Network, Clinical Sciences, Aged, Carbohydrate metabolism, Reproducibility of Results, Radiopharmaceuticals, Sensitivity and Specificity, Lactic Acid, Alzheimer Disease, and Tissue distribution
To investigate, in patients with Alzheimer&#39;s Disease (AD), the possible interplay linking alteration of neuronal energy metabolism, as measured via cerebrospinal fluid (CSF) lactate concentration, to severity of AD... more
To investigate, in patients with Alzheimer&#39;s Disease (AD), the possible interplay linking alteration of neuronal energy metabolism, as measured via cerebrospinal fluid (CSF) lactate concentration, to severity of AD neurodegenerative processes and impairment of cognitive abilities. In this study we measured and correlated CSF lactate concentrations, AD biomarker levels (τ-proteins and β-amyloid) and Mini-Mental State Examination (MMSE) score in a population of drug-naïve patients with AD ranging from mild (MMSE≥21/30) to moderate-severe (MMSE&lt;21/30) cognitive decline. They were compared to healthy controls and patients with vascular dementia (VaD). Patients with AD (n=145) showed a significant increase of CSF lactate concentration compared to controls (n=80) and patients with VaD (n=44), which was higher in mild (n=67) than in patients with moderate-severe AD (n=78). Moreover, we found, in either the whole AD population or both subgroups, a CSF profile in which higher CSF levels of t-τ and p-τ proteins corresponded to lower concentrations of lactate. We verified the occurrence of high CSF lactate levels in patients with AD, which may be ascribed to mitochondria impairment. Hypothesising that τ proteins may exert a detrimental effect on the entire cellular energy metabolism, the negative correlation found between lactate and τ-protein levels may allow speculation that τ toxicity, already demonstrated to have affected mitochondria, could also impair glycolytic metabolism with a less evident increase of lactate levels in more severe AD. Thus, we suggest a dynamic relationship between neuronal energy metabolism, τ proteins and cognitive decline in AD and propose the clinical potential of assessing CSF lactate levels in patients with AD to better define the neuronal brain metabolism damage.
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To the Editor: A late-onset myopathic variant of phosphofructokinase (PFK) deficiency has been described in rare patients of Ashkenazic descent1,2 and proposed as a possible unique disorder on the basis of ethnic and genetic... more
To the Editor: A late-onset myopathic variant of phosphofructokinase (PFK) deficiency has been described in rare patients of Ashkenazic descent1,2 and proposed as a possible unique disorder on the basis of ethnic and genetic considerations.3 A recent article published by Sivakumar et al.4 provides elements to question this hypothesis. These authors described three patients from two generations of an Ashkenazi Jewish family with a partial PFK deficiency and late-onset muscle weakness. A surprising feature of these patients was that, despite a partial (33%) muscle PFK activity detected in vitro, they presented with all the clinical features of complete PFK deficiency, including lifelong exercise intolerance, hyperuricemia, and hemolysis. …
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The etiology of Parkinson's disease (PD) is still not fully clear, but several studies have implicated metals as cofactors of risk. To assess a potential]imbalance in the trace elements concentration of hair of subjects affected by... more
The etiology of Parkinson's disease (PD) is still not fully clear, but several studies have implicated metals as cofactors of risk. To assess a potential]imbalance in the trace elements concentration of hair of subjects affected by PD, the content of Al, Ba, Cd, Co, Cr, Hg, Mn, Me, Ph, Sri, Sr and Zr in 81 patients affected by PD and 17 age-matched controls was determined. Quantification of the elements was performed by inductively coupled plasma mass spectrometry. Results indicated significantly lower levels of Ph in the hair of patients (p <= 0.05) compared with controls. Manganese was slightly higher while Ba, Sri and Sr levels were lower in patients, although these differences were not significant, no variations in Al, Cd, Co, Cr, Mo and Zr levels were observed in PD. Barium and Sr in hair were higher in women than in men in both controls and patients. In addition, again Ba and Sr of patients decreased with age with a p < 0.0 1 for both elements. Finally, a decreased value of Ph with the duration and the severity of the disease and Hg with the severity duration of the pathology were observed.
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Research Interests: Immunohistochemistry, Medicine, Corticotropin Releasing Hormone, Pathophysiology, Stroke, and 15 moreInternal Medicine, Caudate Nucleus, Ischemia, Animals, Male, Brain Ischemia, Rats, Time Factors, Cerebral Blood Flow, Blood Vessel, Middle Cerebral Artery, Cerebral Infarction, Axonal transport, Middle cerebral artery occlusion, and Medical and Health Sciences
Research Interests: Endocrinology, Psychology, Chemistry, Mass Spectrometry, Medicine, and 15 moreCerebrospinal Fluid, Humans, Internal Medicine, Copper, Female, Male, Inductively Coupled Plasma Mass Spectrometry, Metals, Aged, Middle Aged, Oxidative Damage, Biological markers, Neural, Neurosciences, and Parkinson Disease
Neuroscience Department, Polyclinic Tor Vergata, V. le Oxford 81, 00133 Rome, ItalyIntroduction: Listeria innocua is widespread in food and the environment and is considered to bea non-pathogenic bacterium in healthy subjects. To date,... more
Neuroscience Department, Polyclinic Tor Vergata, V. le Oxford 81, 00133 Rome, ItalyIntroduction: Listeria innocua is widespread in food and the environment and is considered to bea non-pathogenic bacterium in healthy subjects. To date, this species has only been associatedwith human diseases in a fatal case of bacteraemia in an elderly patient. Here, we describe a caseof acute meningitis infection caused by this bacterium.Case presentation: Our patient had an increased risk of infection because of treatment withetanercept and a corticosteroid given for rheumatoid arthritis. Etanercept use has been describedpreviously as the possible cause of multiple Listeria monocytogenes infections (to date, fourcases have been described, of which two were cases of arthritis and two of meningitis), butetanercept has never been associated with L. innocua meningitis. In our case, despite rapididentification of the pathogen and proper antibiotic treatment, the patient had an unfavourableoutcome.Conclusion: To the best of our knowledge, this report constitutes the first documentation of acase of meningitis due to L. innocua, and our experience serves as a warning to microbiologistsand clinicians that L. monocytogenes is not the only Listeria sp. that can cause human meningitis.Keywords: etanercept; listeriosis; meningitis.
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Research Interests: Neuroscience, Electrophysiology, Biology, Medicine, Cerebral Cortex, and 15 moreAnimals, Metabotropic Glutamate Receptors, Brain Ischemia, Synaptic Transmission, Neurotoxins, Clinical Sciences, Rats, Huntington disease, Annals, Neurosciences, Interneurons, Glutamate Receptor, Excitatory Postsynaptic Potentials, Corpus striatum, and Kainic acid
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Research Interests: Neurology, Neurosurgery, Medicine, Stroke, Humans, and 15 moreNeuroradiology, Male, Two Stroke Engine, Clinical Sciences, Aged, Single Photon Emission Computed Tomography, Guidance and Counseling Intervention Programs, Midbrain, Neurosciences, Parkinsonism, Translation for Neurological Sciences, Functional Laterality, Neurological Sciences, parkinsonian disorders, and Mesencephalon
Without Abstract
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Parkinson’s disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein, encoded by the SNCA gene. The main neuropathological hallmark of PD is the degeneration of dopaminergic neurons leading to... more
Parkinson’s disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein, encoded by the SNCA gene. The main neuropathological hallmark of PD is the degeneration of dopaminergic neurons leading to striatal dopamine depletion. Trophic support by a neurotrophin called glial-derived neurotrophic factor (GDNF) is also lacking in PD. We performed immunohistochemical studies to investigate neuropathological changes in the basal ganglia of a rat transgenic model of PD overexpressing alfa-synuclein. We observed that neuronal loss also occurs in the dorsolateral part of the striatum in the advanced stages of the disease. Moreover, along with the degeneration of the medium spiny projection neurons, we found a dramatic loss of parvalbumin interneurons. A marked decrease in GDNF, which is produced by parvalbumin interneurons, was observed in the striatum and in the substantia nigra of these animals. This confirmed the involvement of the striatum in the pathop...
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Dystonia is a hyperkinetic movement disorder, whose pathogenesis is related to a network disfunction of basal ganglia, specifically to a disrupted equilibrium between direct and indirect pathways. Phosphodiesterase 10A (PDE10A), a key... more
Dystonia is a hyperkinetic movement disorder, whose pathogenesis is related to a network disfunction of basal ganglia, specifically to a disrupted equilibrium between direct and indirect pathways. Phosphodiesterase 10A (PDE10A), a key enzyme in the catabolism of cAMP and cGMP, is localized within Medium Spiny Neurons in the striatum and in their axon terminals in the substantia nigra pars reticulata and external globus pallidus. Therefore PDE10A may represent a map of the balance between the direct and indirect pathways in normal and pathological basal ganglia conditions. Early-onset torsion dystonia (DYT1), the most common form of dystonia, is an autosomal disease caused by a deletion in the gene encoding protein TorsinA. We investigate changes of PDE10A immunoreactivity in basal ganglia of TorsinA DYT1 mice, a transgenic model of DYT1, comparing results between control mice and mice carrying either human wilde-type torsinA(hWT) or mutant torsinA(hMT). In control mice PDE10A immunoreactivity was observed in neuronal bodies and in the neuropil throughout the caudate-putamen, in the neuropil of the globus pallidus and in substantia nigra pars reticulata. Our study revealed that PDE10A expression was increased in the globus pallidus of hWT mice, while in substantia nigra PDE10 immunoreactivity was overexpressed both in hWT mice and in hMT mice. PDE10A up-regulation may lead to a decreased activation in the indirect striatum-external globus pallidus pathway. The increase of PDE10A also in the substantia nigra suggests that dystonia may express a functional up-regulation of basal ganglia circuits both in the direct and indirect pathway
Research Interests: Neuroscience and Biology
We describe how dopamine loss can affect the catabolism of the second messenger cAMP and cGMP in the basal ganglia, pointing out that Phosphodiesterases 10A (PDE10A) may play a key role in such process. 10 weeks after dopaminergic lesion... more
We describe how dopamine loss can affect the catabolism of the second messenger cAMP and cGMP in the basal ganglia, pointing out that Phosphodiesterases 10A (PDE10A) may play a key role in such process. 10 weeks after dopaminergic lesion in the rat midbrain with 6-OHDA, the cGMP levels are decreased in all dopamine deafferented regions. However, in the same regions: a) &cAMP level show significant increase in the striatum and large variability in the globus pallidus and substantia nigra; b) conversely, cAMP levels are markedly decreased in nucleus accumbens. According to cAMP changes, mRNA and PDE10A expression are down-regulated in the striatum, and in striato-pallidal and striato-nigral projections, while PDE10A is up-regulated in the nucleus accumbens. Therefore, altered cGMP and cAMP steady-states occur in experimental parkinsonism, but only modulation of cAMP catabolism likely relies on dopamine-dependent PDE10A changes. PDE10A downregulation in neurons in the striatum, and in striato-pallidal and striatonigral terminals suggest PDE10A can be involved in dysfunctions of postsynaptic and pre-synaptic modulation of cAMP signaling and synaptic plasticity. Moreover, PDE10A up-regulation in nucleus accumbens secondary to dopamine loss suggests an involvement of PDE10A in mood disorders frequently associated with parkinsonism
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Research Interests:
In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a cost-effective and easy to use sensing tool for customized administration of drugs in Alzheimer's disease. Among several drugs,... more
In the overall scenario of precision medicine, we propose a novel paper-based lab-on-a-chip to deliver a cost-effective and easy to use sensing tool for customized administration of drugs in Alzheimer's disease. Among several drugs, we designed the device for evaluating the efficacy of compounds (e.g. physostigmine, rivastigmine, donepezil) which are able to inhibit in a reversible way the cholinesterase enzyme. Because cholinesterase activity is peculiar to each patient, the administration of customized amount of the drug can improve the treatment efficacy and the quality of patient life, avoiding side effects due to the overdosage. In detail, we exploited Vivid™ Plasma Separation membrane to threat the whole blood sample, filter paper to load the reagents needed for the measurement, and office paper to print electrodes able to measure the butyrylcholinesterase activity, delivering a reagent free analytical tool. The calibration curve of butyrylcholinesterase obtained in blood sample provided linearity between 2 and 12 U/mL, with sensitivity of 0.050 ± 0.004 μA mL/U. The physostigmine, rivastigmine, and donepezil inhibition activities toward the butyrylcholinesterase enzyme were also measured in blood sample with linearity up to respectively 0.5 μM, 25 μM, 30 μM, and detection limits of 0.009 μM, 0.4 μM, 0.3 μM. These results demonstrate the capability of paper-based origami sensors as point of care devices to customize the drug administration in Alzheimer's disease.
Research Interests:
Neuroinflammation is one of the hallmarks of Parkinson’s disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process... more
Neuroinflammation is one of the hallmarks of Parkinson’s disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD – to modulate disease progression – still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early...