What every psychiatrist should know about PANDAS: a review

The term Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) was coined by Swedo et al. in 1998 to describe a subset of childhood obsessive-compulsive disorders (OCD) and tic disorders triggered by group-A beta-hemolytic Streptococcus pyogenes infection. Like adult OCD, PANDAS is associated with basal ganglia dysfunction. Other putative pathogenetic mechanisms of PANDAS include molecular mimicry and autoimmune-mediated altered neuronal signaling, involving calcium-calmodulin dependent protein (CaM) kinase II activity. Nonetheless the contrasting results from numerous studies provide no consensus on whether PANDAS should be considered as a specific nosological entity or simply a useful research framework. Herein we discuss available data that could provide insight into pathophysiology of adult OCD, or might explain cases of treatment-resistance. We also review the latest research findings on diagnostic and treatment

In Vitro Safety/Protection Assessment of Resveratrol and Pterostilbene in a Human Hepatoma Cell Line (HepG2).

The aim of this work was to evaluate in vitro the genotoxic and/or antigenotoxic effects of resveratrol (RESV) and pterostilbene (PTER) on HepG2 cells. Moreover, additional tests were performed to evaluate early and late apoptosis events induced by the tested stilbenes. RESV and PTER did not show any genotoxic activity. As regards antigenotoxicity testing, RESV and PTER showed a typical, U-shaped hormetic dose-response relationship characterized by a biphasic trend with small quantities having opposite effects to large ones. HepG2 cells treated with PTER exhibited a marked increase in early apoptosis (40.1 %) at 250 μM; whereas, the highest concentration tested for both RESV and PTER significantly increased the proportion of HepG2 cells undergoing late apoptosis (32.5 and 51.2 %, respectively). The observed pro-apoptotic activity could, at least in part, explain the hormetic response observed when the compounds were tested for antigenotoxicity ( i.e., in the presence of induced DNA damage)

P03-36 Bradykinesia and mental slowness in patients with obsessive-compulsive disorder

Background:Clinical and experimental findings suggest that Obsessive-Compulsive Disorder (OCD) is due to an abnormality of the cortico-striato-thalamo-cortical circuit. Bradykinesia and mental slowness can be present in patients with basal ganglia disorders affecting the cortico-striato-thalamo-cortical circuit. Aim of this study is to investigate whether bradykinesia and mental slowness are present in patients with OCD.Methods:Participants comprised 19 non-depressed anti-psychotic free patients with OCD.Bradykinesia was assessed with the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). Mental slowness was investigated with the WAIS-R and the Y-BOCS. Psychiatric evaluation was performed with: SCID-I, Y-BOCS, HAMD, HAM-A, and MMPI. Cognitive functions were assessed with the WAIS-R.Results:Bradykinesia and mental slowness were present respectively in the 39% and 89% of the patients. Bradykinesia was positively correlated to Y-BOCS mental slowness score (rho=0.48, p< 0.05), and inversely related to the WAIS-R Performance IQ score (rho=-0.65, p< 0.01). Patients with bradykinesia scored significantly lower in the Similarities and Digit symbol coding WAIS-R subscales as compared to non-bradykinetic patients. in our sample pathological doubt was not associated with IQ measures nor with bradykinesia. Twelve out of 19 patients (63%) showed impairments in the nonverbal function scores.Conclusions:The novel findings of this study is that bradykinesia can be present in patients with OCD, and it is correlated with mental slowness and nonverbal performance impairment. These preliminary data support the notion that dysfunction of basal ganglia is possibly present in OCD patients

Telomerase Mediates Vascular Endothelial Growth Factor-dependent Responsiveness in a Rat Model of Hind Limb Ischemia *

Telomere dysfunction contributes to reduced cell viability, altered differentiation, and impaired regenerative/proliferative responses. Recent advances indicate that telomerase activity confers a pro-angiogenic phenotype to endothelial cells and their precursors. We have investigated whether telomerase contributes to tissue regeneration following hind limb ischemia and vascular endothelial growth factor 165 (VEGF(165)) treatment. VEGF delivery induced angiogenesis and increased expression of the telomerase reverse transcriptase (TERT) and telomerase activity in skeletal muscles and satellite and endothelial cells. Adenovirus-mediated transfer of wild type TERT but not of a dominant negative mutant, TERTdn, significantly induced capillary but not arteriole formation. However, when co-delivered with VEGF, TERTdn abrogated VEGF-dependent angiogenesis, arteriogenesis, and blood flow increase. This effect was paralleled by in vitro evidence that telomerase inhibition by 3'-azido-3'-deoxythymidine in VEGF-treated endothelial cells strongly reduced capillary density and promoted apoptosis in the absence of serum. Similar results were obtained with adenovirus-mediated expression of TERTdn and AKTdn, both reducing endogenous TERT activity and angiogenesis on Matrigel. Mechanistically, neo-angiogenesis in our system involved: (i) VEGF-dependent activation of telomerase through the nitric oxide pathway and (ii) telomerase-dependent activation of endothelial cell differentiation and protection from apoptosis. Furthermore, detection of TERT in activated satellite cells identified them as VEGF targets during muscle regeneration. Because TERT behaves as an angiogenic factor and a downstream effector of VEGF signaling, telomerase activity appears required for VEGF-dependent remodeling of ischemic tissue at the capillaries and arterioles level

Nonmotor symptoms in adult-onset focal dystonia: Psychiatric abnormalities

[No abstract available

Psychiatric disorders in adult-onset focal dystonia: a case-control study

In a single-center, case-control study, we investigated the frequency and types of psychiatric disturbances in 89 consecutive patients with various primary focal dystonias (34 had cervical dystonia (CD), 28 blepharospasm (BPS), 16 laryngeal dystonia (LD), and 11 arm dystonia), 62 healthy control subjects and as controls for BPS, 26 patients with hemifacial spasm (HFS). Patients and controls underwent a full psychiatric evaluation. Diagnosis was based on the structured clinical interview for DSM-IV, obsessive-compulsive disorder (OCD) was assessed with the Yale-Brown Obsessive-Compulsive scale, anxiety with the Hamilton Rating Scale for Anxiety, the severity of depression with the Beck Depression Inventory. Of the 89 patients with focal dystonias studied, 51 patients (57.3%) had a diagnosis of psychiatric disorders compared with only 15 of 62 healthy subjects (24.1%) and 9 of the patients with HFS (34.6%). Depressive disorders were more frequent in the CD and BPS groups than in healthy controls, whereas the frequency of anxiety disorders, OCDs or adjustment disorders approached that of healthy subjects. No difference was found in the frequency of any specific psychiatric disorder in patients with LD and arm dystonia and healthy controls. In 35 of 51 patients who had psychiatric disorders, these started before and in 16 patients after the onset of dystonia. No differences were found in age, dystonia severity, and duration of botulinum toxin treatment between patients with and without psychiatric disturbances. The most common psychiatric features in patients with CD and BPS are depressive disorders

Peptides and peptidomimetics in the p53/MDM2/MDM4 circuitry - a patent review

Introduction: Restoration of the p53 tumor suppressor function is an attractive anticancer strategy. Despite the development of several therapeutics targeting the two main p53 negative regulators, MDM2 and MDM4, no one has yet reached clinical application. In the past, several efforts have been employed to develop more specific and efficient compounds that can improve and/or overcome some of the features related to small molecule compounds (SMC). Peptides and peptidomimetics are emerging as attractive molecules given their increased selectivity, reduced toxicity and reduced tendency to develop tumor-resistance compared to SMC. Areacovered: This article reviews publications and patents (publicly available up to April 2016) for peptides and derivatives aimed to reactivate the oncosuppressive function of p53, with a particular focus on inhibitors of MDM2/MDM4. Emphasis is placed on the efficacy of these compounds compared to the p53-reactivating small molecules developed so far. Expertopinion: A number of promising peptides for p53 reactivation in cancer therapy have been developed. These compounds appear to possess improved features compared to SMC, especially for their ability to simultaneously target the MDM2/MDM4 inhibitors, and their increased specificity

Psychiatric disorders in patients with essential tremor

BACKGROUND: Previous studies have reported that a consistent proportion of patients with Essential Tremor may have psychiatric disorders but it is unclear whether these disorders are increased in frequency as compared to healthy subjects. METHODS: In a case-control study, we adopted the structured interviews for DSM-IV, SCID-I and SCID-II, to investigate psychiatric and personality disorders in 37 ET patients and 34 healthy subjects. As cognitive changes in ET may be a confounding factor we enrolled patients and healthy control subjects without cognitive dysfunction. RESULTS: SCID-I showed that Axis-I psychiatric disorders, mainly depressive disorders, were more frequent in ET patients (20 of 37; 54%) than in healthy subjects (8 of 34; 22%) (p &lt; 0.01). Depressive disorders were more frequent in patients with a family history of ET (p &lt; 0.05) in comparison to patients without a family history. SCID-II disclosed that the frequency of personality disorders was similar in patients with ET and healthy subjects. CONCLUSION: Psychiatric disorders may be associated to the neurological manifestations of ET. Copyright © 2012 Elsevier Ltd. All rights reserved