Synaptic Effects of Palmitoylethanolamide in Neurodegenerative Disorders

Increasing evidence strongly supports the key role of neuroinflammation in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Neuroinflammation may alter synaptic transmission contributing to the progression of neurodegeneration, as largely documented in animal models and in patients’ studies. In the last few years, palmitoylethanolamide (PEA), an endogenous lipid mediator, and its new composite, which is a formulation constituted of PEA and the well-recognized antioxidant flavonoid luteolin (Lut) subjected to an ultra-micronization process (co-ultraPEALut), has been identified as a potential therapeutic agent in different disorders by exerting potential beneficial effects on neurodegeneration and neuroinflammation by modulating synaptic transmission. In this review, we will show the potential therapeutic effects of PEA in animal models and in patients affected by neurodegenerative disorders

Cognitive reserve and Alzheimer's biological continuum: clues for prediction and prevention of dementia

Cognitive reserve is originally an epidemiological concept that encompasses individual abilities to cope with changes. It is considered the result of a balance between processes of cellular damage and repair, and its description raised much interest in predicting and preventing cognitive decline in aging and Alzheimer's disease (AD). Here we discuss the concept of cognitive reserve in light of the recent definition of AD as a biological continuum and suggest that the protection of cognitive reserve may result from efficient synaptic plasticity mechanisms. Despite pathological changes of AD appearing very early during life, long before the onset of cognitive symptoms, different variables act together to keep repair mechanisms effective guaranteeing successful aging as long as environmental enrichment is maintained

Revised gleason grading system is a better predictor of indolent prostate cancer at the time of diagnosis: Retrospective clinical-pathological study on matched biopsy and radical prostatectomy specimens

INTRODUCTION/BACKGROUND: The increase of prostate cancer diagnosis after the introduction of prostate-specific antigen (PSA) screening resulted in overtreatment of patients with low risk tumors. The histological Gleason score (GS) revised in 2005 by the International Society of Urological Pathology (ISUP) is currently the most reliable tool to separate aggressive from indolent prostate cancer. MATERIALS AND METHODS: Using the new 2005 GS criteria we retrospectively evaluated biopsy and surgical samples of 1344 patients who underwent radical prostatectomy in our institution. According to the new GS criteria we then selected 134 patients who would have been suitable for active surveillance at the time of biopsy (at least 2 positive cores, PSA < 10 ng/mL, GS ≤ 6). We finally assessed the accuracy of the revised GS in biopsy to predict indolent cancer in the prostatectomy specimens. RESULTS: The mean GS increased from 6 to 7 after histological revision in biopsy and prostatectomy specimens. Histological revision determined a significant decrease of patients with GS ≤ 6 and an increase of those with GS ≥ 7 (all P < .001). The average of pathologically indolent disease (organ-confined, GS ≤ 6 at surgery, tumor of any volume) significantly decreased after histological revision (P < .001). CONCLUSION: The revised ISUP 2005 criteria for Gleason grading provided better stratification of GS ≤ 6 prostate cancer and improved the accuracy for the histological diagnosis of indolent prostate cancer in biopsy and radical prostatectomy specimens

Effects of palmitoylethanolamide combined with luteoline on frontal lobe functions, high frequency oscillations, and GABAergic transmission in patients with frontotemporal dementia

Background: Frontotemporal dementia (FTD) is a presenile neurodegenerative disease for which there is no effective pharmacological treatment. Recently, a link has been proposed between neuroinflammation and FTD. Objective: Here, we aim to investigate the effects of palmitoylethanolamide (PEA) combined with luteoline (PEA-LUT), an endocannabinoid with anti-inflammatory and neuroprotective effects, on behavior, cognition, and cortical activity in a sample of FTD patients. Methods: Seventeen patients with a diagnosis of probable FTD were enrolled. Cognitive and neurophysiological evaluations were performed at baseline and after 4 weeks of PEA-LUT 700 mg×2/day. Cognitive effects were assessed by Neuropsychiatric Inventory (NPI), Mini-Mental State Examination, Frontal Assessment Battery (FAB), Screening for Aphasia in Neurodegeneration, Activities of Daily Living-Instrumental Activities of Daily Living, and Frontotemporal Lobar Degeneration-modified Clinical Dementia Rating scale. To investigate in vivo neurophysiological effects of PEA-LUT, we used repetitive and paired-pulse transcranial magnetic stimulation (TMS) protocols assessing LTP-like cortical plasticity, short-interval intracortical inhibition, long-interval intracortical inhibition (LICI), and short-latency afferent inhibition. Moreover, we used TMS combined with EEG to evaluate the effects on frontal lobe cortical oscillatory activity. Results: Treatment with PEA-LUT was associated with an improvement in NPI and FAB scores. Neurophysiological evaluation showed a restoration of LICI, in particular at ISI 100 ms, suggesting a modulation of GABA(B) activity. TMS-EEG showed a remarkable increase of TMS-evoked frontal lobe activity and of high-frequency oscillations in the beta/gamma range. Conclusion: PEA-LUT could reduce behavioral disturbances and improve frontal lobe functions in FTD patients through the modulation of cortical oscillatory activity and GABA(B)ergic transmission. Keywords: Brain inflammation; EEG; GABA activity; behavioral symptoms; executive functions; frontotemporal dementia; transcranial magnetic stimulation

Regional Precuneus Cortical Hyperexcitability in Alzheimer's Disease Patients

Objective Neuronal excitation/inhibition (E/I) imbalance is a potential cause of neuronal network malfunctioning in Alzheimer's disease (AD), contributing to cognitive dysfunction. Here, we used a novel approach combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to probe cortical excitability in different brain areas known to be directly involved in AD pathology. Methods We performed TMS-EEG recordings targeting the left dorsolateral prefrontal cortex (l-DLPFC), the left posterior parietal cortex (l-PPC), and the precuneus (PC) in a large sample of patients with mild-to-moderate AD (n = 65) that were compared with a group of age-matched healthy controls (n = 21). Results We found that patients with AD are characterized by a regional cortical hyperexcitability in the PC and, to some extent, in the frontal lobe, as measured by TMS-evoked potentials. Notably, cortical excitability assessed over the l-PPC was comparable between the 2 groups. Furthermore, we found that the individual level of PC excitability was associated with the level of cognitive impairment, as measured with Mini-Mental State Examination, and with corticospinal fluid levels of A beta(42). Interpretation Our data provide novel evidence that precuneus cortical hyperexcitability is a key feature of synaptic dysfunction in patients with AD. The current results point to the combined approach of TMS and EEG as a novel promising technique to measure hyperexcitability in patients with AD. This index could represent a useful biomarker to stage disease severity and evaluate response to novel therapies. ANN NEUROL 202

Prognostic factors of kidney tumors in T3 stage: role of perirenal fat infiltration, renal sinus infiltration and venous thrombosis

none15noneRocca GC;Schiavina R;BRUNOCILLA E.;Garofalo M;Bertaccini A;Concetti S;Saraceni G;Chessa F;Baccos A;Zukerman Z;Pultrone CV;Passaretti G;Rossi MS;Romagnoli D;Martorana GRocca GC;Schiavina R;BRUNOCILLA E.;Garofalo M;Bertaccini A;Concetti S;Saraceni G;Chessa F;Baccos A;Zukerman Z;Pultrone CV;Passaretti G;Rossi MS;Romagnoli D;Martorana