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Levodopa/Carbidopa Intestinal Gel for Treatment of Advanced Parkinson’s Disease: An Update on the Effects of Cognitive Functions

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Advances in Parkinson's Disease 2017年第1期6卷 13-23页

作者： Pamela Latino Stefania Tagliente clelia Pellicano Morena Giovannelli Francesco E. Pontieri Department of Neuroscience Mental Health and Sensory Organs (NeSMOS) “Sapienza” University Rome Italy Department of Clinical and Behavioral Neurology “Santa Lucia Foundation” IRCCS Rome Italy Unit of Neurology Sant’Andrea Hospital Rome Italy

Cognitive impairment is a frequent non-motorsymptom of Parkinson’s disease (PD). In early disease stage, this takes the features of dysexecutive syndrome, and is mostly dependent on derangement of frontostriatal circuitries. In advanced stages, worsening of dysexecutive symptoms is accompanied by disorientation and memory deficit leading to dementia in 30% of cases, due to multiple neurotransmitter derangement. Dysexecutive symptoms in the early stages of PD may benefit from dopamine replacement therapy (DRT). Conversely, severe cognitive symptoms in more advanced stages are frequently aggravated by DRT. In particular, pulsatile stimulation of dopaminergic receptors by orally administered levodopa (LD) plays a significant negative role on cognitive and neuropsychiatric symptoms in advanced PD. The introduction of a gel of LD-carbidopa for continuous intestinal administration (LCIG) allows marked stabilization of plasma LD concentrations and provides benefit on motor fluctuations and dyskinesia of significantly greater magnitude than conventional oral administration in advanced PD patients. The results from several preliminary studies suggest that efficacy of LCGI on motor symptoms may be accompanied by good tolerability and potential benefit on several non-motor symptoms, including cognitive impairment. Future studies with longer observation period and larger cohorts are advised to confirm these preliminary observations.

关键词： Cognition Dementia Dopamine Replacement Therapy Duodopa Levodopa Parkinson’s Disease

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Why do we not reverse the path?Stress can cause depression,reduction of brain-derived neurotrophic factor and increased inflammation

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World Journal of Psychiatry 2022年第9期12卷 1264-1267页

作者： Angelo Emilio Claro clelia Palanza Marianna Mazza Alessandro Rizzi Linda Tartaglione Giuseppe Marano Giovanna Muti-Schuenemann Marta Rigoni Paola Muti Alfredo Pontecorvi Luigi Janiri Gabriele Sani Dario Pitocco Department of Geriatrics Neuroscience and OrthopedicsFondazione Policlinico Universitario A.Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Istituto Italiano di Antropologia IsiTaRome 00185Italy Department of Medical and Surgical Sciences Policlinico Universitario A.Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Health Research Methods Evidence and Impact DepartmentMcMaster UniversityOntario K9V 0A0Canada Department of Biomedical Surgical and Dental SciencesUniversity of MilanMilan 20126Italy Department of Endocrine-Metabolic and Dermo-Rheumatology Fondazione Policlinico Universitario A.Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Department of Medical and Surgical Sciences Fondazione Policlinico Universitario A.Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy

The aim of this paper is to describe the direction of the link between stress,depression,increased inflammation and brain-derived neurotrophic factor(BDNF)*** hypothesize that severe stress or prolonged stress can be the driving factor that promote the onset of *** stress and depression,if not resolved over time,activate the production of transcription factors that will switch on pro-inflammatory genes and translate them into *** cascade fosters systemic chronic inflammation and reduced plasma BDNF *** people with depression have a 60%increased risk of developing type 2diabetes(T2D)and show high levels of inflammation and low levels of BDNF,we hypothesize possible reasons that might explain why T2D,depression and dementia are often associated in the same patient.

关键词： Depression Inflammation Brain-derived neurotrophic factor Type 2 diabetes mellitus Dementia Psychological stress

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Hepatocellular carcinoma and microbiota:Implications for clinical management and treatment

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World Journal of Hepatology 2022年第7期14卷 1319-1332页

作者： Dario Spanu Andrea Pretta Eleonora Lai Mara Persano clelia Donisi Stefano Mariani Marco Dubois Marco Migliari Giorgio Saba Pina Ziranu Valeria Pusceddu Marco Puzzoni Giorgio Astara Mario Scartozzi Medical Oncology Unit University Hospital and University of CagliariMonserrato 09042CagliariItaly

Gut microbiota plays an essential role in host *** is involved in several physiological processes such as nutrients digestion and absorption,maintenance of intestinal epithelial barrier integrity and immune system *** the gut microbiota is assumed to play a crucial role in many gastrointestinal,pancreatic and liver *** role in hepatic carcinogenesis is also gaining increasing interest,especially regarding the development of therapeutic *** studies are highlighting a link between some bacterial strains and liver disease,including hepatocellular carcinoma(HCC).Indeed,HCC represents an interesting field of research in this perspective,due to the gut-liver axis,to the implication of microbiota in the immune system and to the increasing number of immunotherapy agents investigated in this ***,the assessment of the role of microbiota in influencing clinical outcome for patients treated with these drugs is becoming of increasing *** review aims to give an overview on the relationship between microbiota and HCC development/progression and *** focus on potential implications on the available treatment strategies and those under study in the various stages of *** highlight the pathogenic mechanisms and investigate the underlying molecular pathways ***,we investigate the potential prognostic and/or predictive role of microbiota for target therapies,immune checkpoint inhibitors and loco-regional ***,given the limitation of current treatments,we analyze the gut microbiota-mediated therapies and its potential options for HCC treatment focusing on fecal microbiota transplantation.

关键词： Hepatocellular carcinoma Gut microbiota Gut-liver axis Fecal microbiota transplantation Carcinogenesis Immune checkpoint inhibitors

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Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing

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Regenerative Biomaterials 2021年第5期8卷 75-86页

作者： Alessia Ajovalasit Carlos Redondo-Go´mez Maria Antonietta Sabatino Babatunde OOkesola Kristin Braun Alvaro Mata clelia Dispenza Dipartimento di Ingegneria(DI) Universitadegli Studi di PalermoViale delle ScienzeEdificio 6Palermo 90128Italy School of Engineering&Materials Science Queen Mary University of LondonLondon E14NSUK Institute of Bioengineering Queen Mary University of LondonLondon E14NSUK Blizard Institute Barts and The London School of Medicine and DentistryThe Blizard Building4 Newark StreetLondon E12ATUK School of Pharmacy University of NottinghamNottingham NG72RDUK Department of Chemical and Environmental Engineering University of NottinghamNottingham NG72RDUK Biodiscovery Institute University of NottinghamNottinghamNG72RDUK Istituto di Biofisica(IBF) Consiglio Nazionale Delle Ricerche(CNR)Via U.La Malfa 153Palermo 90146Italy

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound *** work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular *** this aim,the co-assembly behaviour of a carboxylated variant of xyloglucan(CXG)with a peptide amphiphile(PA-H3)has been investigated to generate hierarchical constructs with tuneable molecular composition,structure,and *** electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and *** a higher concentration,CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by smallamplitude oscillatory shear rheological measurements and compression tests at different CXG/PAH3 ratios.A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model.

关键词： self-assembly peptide nanofiber hydrogel wound healing skin tissue engineering

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Circulating tumour DNA in gastrointestinal cancer in clinical practice:Just a dream or maybe not?

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World Journal of Clinical Oncology 2022年第12期13卷 980-983页

作者： Andrea Pretta Eleonora Lai clelia Donisi Dario Spanu Pina Ziranu Valeria Pusceddu Marco Puzzoni Elena Massa Mario Scartozzi Medical Oncology Unit University Hospital and University of CagliariMonserrato 09042CagliariItaly

The evaluation of circulating tumor DNA(ctDNA)is increasingly integrated into the management of diagnosis and treatment of gastrointestinal cancer as it represents an innovative and minimally invasive biomarker that could allow us to reach clinical needs not met yet in randomized clinical *** research provided an interesting overview of the role of circulating tumor DNA in gastric,biliary,liver,pancreatic,and colorectal *** regarding upper gastrointestinal tumors are currently not practice *** detection rates are low in the early stages,while in advanced stages ctDNA is useful for molecular tracking *** of the evidence comes from colorectal cancer studies,where ctDNA was evaluated both in the early and advanced stages with the postsurgery minimal residual disease assessment and the response assessment,*** qualifies as a promising tool in the era of precision medicine,with potential applications in the entire management of gastrointestinal cancer *** evidence is needed to establish which setting may be influenced greatly by liquid biopsy in clinical practice.

关键词： Circulating tumor DNA Gastrointestinal cancer Liquid biopsy Esophageal cancer Gastric cancer Liver cancer Bile duct cancer Pancreatic cancer Colorectal cancer

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Evaluation of Xpert MTB/RIF Ultra for Diagnosis of Extrapulmonary Tuberculosis: A Retrospective Analysis in a Low-Tuberculosis Prevalence Setting

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Journal of Tuberculosis Research 2021年第3期9卷 219-229页

作者： Annalisa Del Giudice Rossella Perna Teresa Baldoni Francesco Scarano Annunziata De Rosa Agostina Pontarelli Mario De Marco Martha Alicia Falca clelia Di Tella Luigi Atripaldi Sergio Alfonso Harari Andrea Bianco Roberto Parrella UOC Microbiologia e Virologia Hospital Cotugno AORN Ospedali dei Colli Naples Italy UOC Respiratory Infectious Diseases Unit Hospital Cotugno AORN Ospedali dei Colli Naples Italy Department of Medical Sciences San Giuseppe Hospital MultiMedica IRCCS and Department of Clinical Sciences and Community Health University of Milan Milan Italy Department of Translational Medical Sciences University of Campania “L. Vanvitelli”/Hospital Monaldi Naples Italy

Background: Extrapulmonary tuberculosis (EPTB) remains difficult to diagnose because the clinical specimens to be examined are often paucibacillary and obtained with difficulty from inaccessible sites. An updated Xpert® MTB/RIF Ultra (Ultra) test has been designed and licensed to improve sensitivity in the detection of Mycobacterium tuberculosis complex. The aim of the present study is to evaluate the performance of Ultra assay for the clinical diagnosis of EPTB in a low tuberculosis prevalence country. Methods: A retrospective analysis was performed at “A. O dei Colli” of Naples on consecutive extrapulmonary specimens for EPTB across a three-year period. All different types of extrapulmonary specimens were tested for EPTB by smear microscopy, culture and Ultra assay in accordance with relevant guidelines.

关键词： Extrapulmonary Tuberculosis Molecular Diagnosis Mycobacterium tuberculosis Xpert® MTB/RIF Ultra

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Short- and long-term effects of silver nanoparticles on human microvascular endothelial cells

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World Journal of Biological Chemistry 2014年第4期5卷 457-464页

作者： Sara Castiglioni clelia Caspani Alessandra Cazzaniga Jeanette AM Maier Dipartimento di Scienze Biomediche e Cliniche Luigi Sacco Università di Milano Milano 20157 Italy

AIM: To study the response to silver nanoparticles(Ag NP) of human microvascular endothelial cells, protagonists of angiogenesis. METHODS: We cultured human microvascular endothelial cells and endothelial colony-forming cells in their corresponding growth medium. Stock solutions of Ag NP were prepared in culture medium and sonicated before use. They were added at different concentrations and for different times to culture media. The toxicity of Ag NP was investigated by measuring the reduction of yellow tetrazolium salt to dark purple formazan(MTT assay) at 575 nm. After staining with trypan blue, cell proliferation was assessed by counting viable cells. The lactate dehydrogenase leakage assay was performed on culture media by following the oxidation of NADH to NAD+ and monitoring the reaction kinetically at 340 nm. Reactive oxygen species production was quantified using 2'-7'-dichlorofluorescein diacetate. The alkaline comet assay was performed after mixing the cells with low melting-point agarose. Electrophoresis was then conducted and the samples were stained with ethidium bromide and analyzed with a fluorescence ***: Ag NP are cytotoxic in a dose and time dependent fashion for HMEC. At high concentrations, Ag NP determine loss of membrane integrity as demonstrated by the increased activity of lactate dehydrogenase in the culture medium. Ag NP rapidly stimulate the formation of free radicals. However, pre-incubation with Trolox, apocynin, or N-acetyl-L-cysteine, antioxidants which have different structure and act through different mechanisms, is not sufficient to prevent cytotoxicity. Ag NP also induce DNA damage dose-dependently, as shown by comet assay. When exposed to sublethal concentrations of Ag NP for long times, the cells remain viable but are growth retarded. Interestingly, removal of Ag NP partially rescues cell growth. Also genotoxicity is reversible upon removal of Ag NP from culture medium, suggesting that no permanent modifications oc

关键词： Endothelial cells Nanoparticles Genotoxicity Cytotoxicity Angiogenesis

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