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Pulmonary administration of functionalized nanoparticles significantly reduces beta-amyloid in the brain of an Alzheimer＇s disease murine model

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Nano Research 2016年第7期9卷 2190-2201页

作者： Giulio Sancini Roberta Dal Magro Francesca Ornaghi Claudia Balducci Gianluigi Forloni marco gobbi Mario Salmona Francesca Re Nanomedicine Center School of Medicine and Surgery University of Milano-Bicocca via Cadore 48 20900 Monza (MB) Italy Department ofNeuroscience IRCCS-Istituto di Ricerche Farmacologiche Mario Negri via La Masa 19 20159 Milano Italy Department of Biochemistry and Molecular Pharmacology IRCCS-Istituto di Ricerche Farmacologiche Mario Negri via La Masa 19 20159 Milano Italy

Treatment options for Alzheimer＇s disease （AD） are limited because of the inability of drugs to cross the blood-brain barrier （BBB）. A promising strategy to overcome this obstacle is the use of nanoparticles （NPs）. Previously, we showed that intraperitoneal administration of liposomes functionalized with phosphatidic acid and an ApoE-derived peptide （mApoE-PA-LIP） reduces brain beta-amyloid （A） burden and ameliorates impaired memory in AD mice. Here, we investigated lung administration as an alternative, non-invasive NP delivery route for reaching the brain. Our results show that mApoE-PA-LIP were able to cross the pulmonary epithelium （[C]-PA permeability = 6.5 ＋ 2.0 × 10^4 cm/min） in vitro and reach the brain （up to 0.6 μg PA/g brain） following in vivo intratracheal instillations. Lung administration of mApoE-PA-LIP to AD mice significantly decreased total brain Aβ （-60%; p 〈 0.05） compared to untreated mice. These results suggest that pulmonary administration could be exploited for brain delivery of NPs designed for AD therapy.

关键词： ApoE-derived peptide lung administration nanoparticles Alzheimer's disease liposomes

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Glacial biodiversity of the southernmost glaciers of the European Alps(Clapier and Peirabroc,Italy)

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Journal of Mountain Science 2022年第8期19卷 2139-2159页

作者： Barbara VALLE Mauro gobbi Marta TOGNETTI Marina Serena BORGATTI Chiara COMPOSTELLA Paolo PANTINI marco CACCIANIGA Universitàdegli Studi di Milano Department of BiosciencesVia Celoria 2620133 MilanoItaly MUSE-Science Museum of Trento Research and Museum Collections OfficeClimate and Ecology UnitCorso del Lavoro e della Scienza338122 TrentoItaly Universitàdegli Studi di Milano Dipartimento di Scienze della Terra"A.Desio"Via Mangiagalli 3420133 MilanoItaly Museo Civico di Scienze Naturali"E.Caffi" Piazza della Cittadella1024129 BergamoItaly

We applied a multi-taxa approach integrating the co-occurrence of plants,ground beetles,spiders and springtails with soil parameters(temperatures and chemical characteristics)in order to describe the primary succession along two glacier forelands in the Maritime Alps(Italy),a hotspot of Mediterranean *** compared these successions to those from Central Alps:Maritime glacier forelands markedly differ for their higher values of species richness and species *** to our expectation,Maritime glacier forelands follow a‘replacement change model’,like continental succession of Inner Alps and differently from other peripheral *** propose that the temperatures along these Mediterranean glacier forelands are warmer than those along other Alpine glacier forelands,which promote the faster species ***,we found that early and mid successional stages of the investigated glaciers are richer in cold-adapted and endemic species than the later ones:we confirmed that the‘replacement change’model disadvantages pioneer,cold-adapted *** the overall correspondence among coldadapted and endemic species,the most threatened in this climate phase,our results raise new concerns about the extinction risk of these *** also describe supraglacial habitat of Maritime glaciers demonstrating that supraglacial debris represents an environment decoupled from the regional climate and may have an important role as refugium for coldadapted and hygrophilous plant and animal species,whose survival can be threatened by climate change and by a rapid ecological succession in the adjacent forelands.

关键词： Arthropod communities Cold-adapted species Glacier forelands Plant communities Primary succession

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Quantitative alpha-defensin testing: Is synovial fluid dilution important?

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World Journal of Orthopedics 2022年第8期13卷 760-767页

作者： Rodrigo Calil Teles Abdo Riccardo Gomes gobbi Chilan Bou Ghosson Leite Sandra Gofinet Pasoto Elaine Pires Leon Ana Lucia Lei Munhoz Lima Eloisa Bonfa JoséRicardo Pécora marco Kawamura Demange Instituto de Ortopedia e Traumatologia Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSao Paulo 05403-010Brazil Orthopaedic Department HCor-Hospital do CoraçãoSao Paulo 04004-030Brazil Division of Rheumatology Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSao Paulo 05403-010Brazil

BACKGROUND Alpha-defensin has been widely studied for the diagnosis of periprosthetic joint infection(PJI).However,there is a lack of detailed information regarding the proper laboratory technique of the enzyme-linked immunosorbent assay(ELISA)method,such as sample *** To assess the influence of dilution in the synovial fluid during ELISA for the diagnosis of knee PJI;and determine which dilution presents a better *** Forty samples of synovial fluid from arthroplasty knees were included,17 in the infected group and 23 in the aseptic group,according to Musculoskeletal Infection Society ***,five synovial fluid samples from each group were assessed for quantitative analysis of alpha-defensin using *** dilution ratios(1:10,1:100,1:500,1:1000 and 1:5000)were tested based on the predetermined cutoff value of 5.2 mg/*** dilutions that performed better were used to compare the results of all *** For infected cases,a gradual increase in the dilution of synovial fluid samples led to an equivalent increase in alpha-defensin *** same was not observed in the aseptic *** 1:1000 and 1:5000 dilutions presented satisfactory results to differentiate infected and aseptic *** analyses were performed using 1:1000 and 1:5000 for all 40 *** 1:1000 dilution resulted in a sensitivity of 88.2%(95%CI,66%-98%)and specificity of 95.7%(95%CI,79%-99%),whereas the 1:5000 dilution presented a sensitivity of 94.1%(95%CI,73%-99%)and a specificity of 100%(95%CI,86%-100%).CONCLUSION The synovial fluid dilution had an important influence on the alpha-defensin ELISA *** of 1:5000 showed the best performance for the diagnosis of knee *** results of this study set the basis for a more reliable and reproducible alpha-defensin ELISA during the investigation of PJI,contributing to the expansion of this technique in different treatment centers worldwide.

关键词： Alpha-defensin Enzyme-linked immunosorbent assay Periprosthetic joint infection Laboratory findings

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Acute heart failure in elderly patients:a review of invasive and non-invasive management

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Journal of Geriatric Cardiology 2021年第7期18卷 560-576页

作者： Gregorio Tersalvi Alessio Gasperetti marco Schiavone Jeroen Dauw Cecilia gobbi Marialessia Denora Joel Daniel Krul Giacomo Maria Cioffi Gianfranco Mitacchione Giovanni B.Forleo Department of Internal Medicine Hirslanden Klinik St.AnnaLucerneSwitzerland Cardiology Unit ASST-Fatebenefratelli SaccoLuigi Sacco University HospitalMilanItaly Department of Cardiology Ziekenhuis Oost-LimburgGenkBelgium Doctoral School for Medicine and Life Sciences Hasselt UniversityDiepenbeekBelgium Institut Cardiovasculaire de Caen Hôpital PrivéSaint MartinCaenFrance Division of Cardiology Fondazione Cardiocentro TicinoLuganoSwitzerland Division of Cardiology Heart CenterLuzerner KantonsspitalLucerneSwitzerland

Acute heart failure(AHF)is a major cause of unplanned hospitalisations in the elderly and is associated with high *** prevalence has grown in the last years due to population aging and longer life expectancy of chronic heart failure *** international societies have provided guidelines for the management of AHF in the general population,scientific evidence for geriatric patients is often lacking,as these are underrepresented in clinical *** have a different risk profile with more comorbidities,disability,and frailty,leading to increased morbidity,longer recovery time,higher readmission rates,and higher ***,therapeutic options are often limited,due to unfeasibility of invasive strategies,mechanical circulatory support and cardiac ***,the in-hospital management of AHF should be tailored to each patient's clinical situation,cardiopulmonary condition and geriatric *** care should be considered in some cases,in order to avoid unnecessary diagnostics and/or *** discharge,a strict follow-up through outpatient clinic or telemedicine is can improve quality of life and reduce rehospitalisation *** aim of this review is to offer an insight on current literature and provide a clinically oriented,patient-tailored approach regarding assessment,treatment and follow-up of elderly patients admitted for AHF.

关键词： patients mortality invasive

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Performance of alpha-defensin lateral flow test after synovial fluid centrifugation for diagnosis of periprosthetic knee infection

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World Journal of Orthopedics 2021年第8期12卷 565-574页

作者： Rodrigo Calil Teles Abdo Riccardo Gomes gobbi Chilan Bou Ghosson Leite Sandra Gofinet Pasoto Elaine Pires Leon Ana Lucia Lei Munhoz Lima Eloisa Bonfa José Ricardo Pécora marco Kawamura Demange Instituto de Ortopedia e Traumatologia Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSao Paulo 05403-010Brazil Division of Rheumatology Faculdade de Medicina da Universidade de São PauloSao Paulo 01246-903Brazil

BACKGROUND The quantitative alpha-defensin enzyme-linked immunosorbent assay(ELISA)demands a prior synovial fluid centrifugation,whereas this processing is not routinely required prior to the alpha-defensin lateral flow *** To evaluate whether a prior synovial fluid centrifugation could lead the lateral flow performance to achieve comparable results to ELISA during periprosthetic joint infection(PJI)*** Fifty-three cases were included in this study:22 classified as PJI and 31 classified as aseptic cases,according to Musculoskeletal Infection Society 2013 *** fluid samples were submitted to centrifugation,and the supernatant was evaluated by ELISA and lateral flow *** sensitivity(SE),specificity(SP)and accuracy of each method were calculated as well as the agreement between those two *** In all of the 31 samples from aseptic patients,alpha-defensin ELISA and lateral flow tests showed negative results for *** the 22 infected patients,the lateral flow test was positive in 19 cases(86.4%)and the ELISA was positive in 21(95.5%).Sensibility,SP and accuracy were,respectively,86.4%(95%CI:65.1%-97.1%),100%(95%CI:88.8%-100%)and 93.2%(95%CI:82.8%-98.3%)for the lateral flow test and 95.5%(95%CI:77.2%-99.9%),100%(95%CI:88.8%-100%)and 98.1%(95%CI:89.9%-100%)for *** agreement of 96.2%between those methods were *** statistical difference was found between them(P=0.48).CONCLUSION Alpha-defensin lateral flow test showed high SE,SP and accuracy after a prior synovial fluid centrifugation,achieving comparable results to *** the lower complexity of the lateral flow and its equivalent performance obtained in this condition,a prior centrifugation might be added as a valuable step to enhance the PJI diagnosis.

关键词： Alpha-defensin Alpha-defensin lateral flow Periprosthetic joint infection

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