Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

COVID-19 pandemic in the intensive care unit:Psychological implications and interventions,a systematic review

BACKGROUND The coronavirus disease 2019(COVID-19) pandemic produced changes in intensive care units(ICUs) in patient care and health organizations. The pandemic event increased patients’ risk of developing psychological symptoms during and after hospitalisation. These consequences also affected those family members who could not access the hospital. In addition, the initial lack of knowledge about the virus and its management, the climate of fear and uncertainty, the increased workload and the risk of becoming infected and being contagious, had a strong impact on healthcare staff and organizations. This highlighted the importance of interventions aimed at providing psychological support to ICUs, involving patients, their relatives, and the staff;this might involve the reorganisation of the daily routine and rearrangement of ICU staff duties.AIM To conduct a systematic review of psychological issues in ICUs during the COVID-19 pandemic involving patients, their relatives, and ICU staff.METHODS We investigated the PubMed and the ClinicalTrials.gov databases and found 65 eligible articles,upon which we commented.RESULTS Our results point to increased perceived stress and psychological distress in staff, patients and their relatives and increased worry for being infected with severe acute respiratory syndrome coronavirus-2 in patients and relatives. Furthermore, promising results were obtained for some psychological programmes aiming at improving psychological measures in all ICU categories.CONCLUSION As the pandemic limited direct inter-individual interactions, the role of interventions using digital tools and virtual reality is becoming increasingly important. All considered, our results indicate an essential role for psychologists in ICUs.

Enteroscopy in children and adults with inflammatory bowel disease

Inflammatory bowel disease(IBD)includes Crohn’s disease(CD),ulcerative colitis and unclassified entities.CD commonly involves the terminal ileum and colon but at the time of diagnosis it can be confined to the small bowel(SB)in about 30%of the patients,especially in the young ones.Management of isolated SB-CD can be challenging and objective evaluation of the SB mucosa is essential in differentiating CD from other enteropathies to achieve therapeutic decisions and to plan the follow-up.The introduction of cross-sectional imaging techniques and capsule endoscopy(CE)have significantly expanded the ability to diagnose SB diseases providing a non-invasive test for the visualization of the entire SB mucosa.The main CE limitations are the low specificity,the lack of therapeutic capabilities and the impossibility to take biopsies.Device assisted enteroscopy(DAE)enables histological confirmation when traditional endoscopy,capsule endoscopy and cross-sectional imaging are inconclusive and also allows therapeutic interventions such as balloon stricture dilation,intralesional steroid injection,capsule retrieval and more recently stent insertion.In the current review we will discuss technical aspect,indications and safety profile of DAE in children and adults with IBD.

Early onset versus late onset in Alzheimer’s disease: What is the reliable cut-off?

Objective: As the literature on conventional criteria for discriminating early-onset (EO) from late-onset (LO) Alzheimer’s disease (AD) is sparse and controversial, the aim of this study was to establish a precise age at onset (AAO) criterion, by using a specific statistical procedure, and to describe the clinical characteristics of the two sub-groups. Methods: Admixture analysis was performed to establish the AAO cut-off in a multi-center study including 2000 AD patients consecutively recruited in eight Italian Memory Clinics. None of the patients were taking acetylcholinesterase inhibitors, antipsychoticor anti-depressant drugs. At the first diagnosticvisit, they were administered the Mini Mental StateExamination, the Basic and Instrumental Activities of Daily Living and the Neuropsychiatric Inventorytoassess clinical phenomenology. Results: Using a specific statistical procedure, we established that AAO that discriminated EO-from LO-AD was 66. Compared with the LO-AD group, the EO-AD group showed longer duration of illness and a higher educational level as well as less severe functional impairment and delusions. Conclusions: Differences in sociodemographic and clinical characteristics, such as duration of illness, education and delusion severity, suggested the involvement of different pathogenic processes. Additional studies are needed to further investigate the mechanisms underlying the disorder in the two sub-groups of AD patients.

Memantine: New prospective in bipolar disorder treatment

We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manicdepressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity(mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon(dopamine receptor desensitization) and an increased immobility time(depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action(at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in maniclike symptoms occurring in psychiatric disorders other than bipolar. Limitations: A randomized controlled clinical trial is needed to confirm our naturalistic observations.Conclusion: We believe that this review presents enough pharmacological and clinical information to consider the administration of memantine in the treatment of bipolar disorders that no respond to standard mood stabilizers.

Respiratory syncytial virus and adenovirus in acute lower respiratory infections in hospitalized infants and children

Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than human adenovirus (HAdV) in cold seasons;recent data suggest that oropharyngeal swabs more frequently contain HAdV than RSV. Knowing more about virus detection with oropharyngeal swabs, seasonal fluctuations and age-related distribution of RSV and HAdV would help treat children hospitalized for LRTI more effectively. We investigated the seasonal virus-related frequency (as assessed by oropharyngeal swabs) and environmental and clinical features in infants and children hospitalized for LRTI from autumn to spring. Methods: We studied 98 subjects hospitalized for LRTI in our Pediatric Unit, from November 2006 to May 2007. RSV and HAdV in oropharyngeal swabs were assessed by real-time polymerase chain reaction (PCR) assay. Results: PCR assays more frequently detected HAdV (29.6% of patients) than RSV (25.5%). The seasonal incidence also differed (RSV, narrow peak in December and HAdV, wide peak from April to May). Most patients infected with RSV were aged 2 yrs or younger (23/25: 88%);no difference was found in age between subjects who tested HAdV-positive (13/29: 45%) or undetectable-virus (23/44: 52%). Bronchiolitis was more frequently associated with RSV than HAdV or undetectable-virus oropharyngeal swabs. No difference was found in risk factors (school attendance, atopic parents, exposure to cigarette smoking, home dampness or exposure to animals) or clinical features (vital parameters or duration of hospital stay) among the three viral groups. Conclusions: Our findings show a high frequency of HAdV-positive oropharyngeal swabs during acute LRTIs in infants and children and differences in the seasonal distribution of RSV and HAdV in Rome.