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41.
Antioxidant properties of ursodeoxycholic acid 总被引:5,自引:0,他引:5
Lapenna D Ciofani G Festi D Neri M Pierdomenico SD Giamberardino MA Cuccurullo F 《Biochemical pharmacology》2002,64(11):1661-1667
We have investigated potential antioxidant properties of the clinically relevant bile acid UDCA, which reaches therapeutic concentrations up to 0.09 and 29 mM, respectively, in human plasma and bile. UDCA was an excellent scavenger of OHz.rad; generated by FeCl(3)-EDTA, H(2)O(2) and ascorbate in the deoxyribose oxidation test, showing IC(min) and IC(50) values of 0.02 and 0.2 mM, respectively, and a second-order rate constant for reaction with OHz.rad; of 2+/-0.1 x 10(10)M(-1)s(-1). Notably, the drug could enhance at 1.5 mM concentration the antioxidant capacity of human bile against OHz.rad;-induced deoxyribose oxidation. UDCA also showed antioxidant effects in the deoxyribose test performed with nonchelated iron ions, such as Fe(2+) plus H(2)O(2) (IC(min): 7 mM, IC(50): 20 mM) or Fe(3+) plus H(2)O(2) and ascorbate (IC(min): 0.3 mM, IC(50): 5 mM), and inhibited ferrozine-Fe(2+) and desferrioxamine-Fe(3+) complexes formation with IC(50) values of, respectively, 12 and 0.3 mM, indicating that the drug interacts more with iron(III) than with iron(II). Moreover, UDCA significantly inhibited phospholipid liposome peroxidation induced by the OHz.rad;-generating system FeCl(3)-EDTA, H(2)O(2) and ascorbate (IC(min): 0.75 mM, IC(50): 3 mM), and by peroxyl radicals generated in the aqueous phase by AAPH (IC(min): 8 mM, IC(50): 14 mM). UDCA, even at 25 mM concentration, was ineffective on the lipoperoxidation mediated by Fe(2+) alone, but at the same concentration counteracted significantly that by Fe(3+) plus ascorbate, further pointing to its preferential antioxidant interaction with iron(III).In conclusion, UDCA has direct antioxidant properties, which are especially relevant against Fe(3+)- and OHz.rad;-dependent biomolecular oxidative damage; such properties are evident at therapeutically relevant drug concentrations, suggesting that UDCA could act as an antioxidant in vivo. 相似文献
42.
Nappi L Matteo M Giardina S Rosenberg P Indraccolo U Greco P 《Archives of gynecology and obstetrics》2008,278(1):61-63
BACKGROUND: Giant myomas of the uterus are uncommon, particularly in developed countries. CASE: This report illustrates a case of a woman with a bilobated giant myoma of the uterus weighed in total 27.7 kg. The patient had an abdominal distension first noted 18 months before and the personal history evidenced difficulties in walking and tiredness. Abdominal hysterectomy and bilateral salpingo-oophorectomy were carried out. CONCLUSIONS: The knowledge of the different clinical manifestation of these myomas may allow to face that with adequate perioperative care, in order to assure a carefully and successfully surgery, although sometimes a benign pathology may be not easy to suspect in a first time. 相似文献
43.
Pablo Canales-Herrerias Etienne Crickx Matteo Broketa Aurlien Sokal Guilhem Chenon Imane Azzaoui Alexis Vandenberghe Angga Perima Bruno Iannascoli Odile Richard-Le Goff Carlos Castrillon Guillaume Mottet Delphine Sterlin Ailsa Robbins Marc Michel Patrick England Gael A. Millot Klaus Eyer Jean Baudry Matthieu Mahevas Pierre Bruhns 《The Journal of clinical investigation》2022,132(12)
The major therapeutic goal for immune thrombocytopenic purpura (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. Eighty percent of patients with ITP possess anti–integrin αIIbβ3 IgG autoantibodies that cause platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in approximately 50% of patients to recover a normal platelet count after anti-CD20 rituximab-mediated B cell depletion and splenectomy suggests that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SCs) reside in other anatomical compartments. We analyzed more than 3,300 single IgG-SCs from spleen, bone marrow, and/or blood of 27 patients with ITP, revealing high interindividual variability in affinity for αIIbβ3, with variations over 3 logs. IgG-SC dissemination and range of affinities were, however, similar for each patient. Longitudinal analysis of autoreactive IgG-SCs upon treatment with the anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti–αIIbβ3 IgG-SCs in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies. 相似文献
44.
Paolo De Pasquale Erasmo Rubino Daniele Borzelli Matteo Peditto Enrico Nastro Siniscalchi Francesco Saverio De Ponte Giacomo Oteri Andrea dAvella 《Materials》2022,15(11)
Assessing maximum voluntary bite force is important to characterize the functional state of the masticatory system. Due to several factors affecting the estimation of the maximum bite force, a unique solution combining desirable features such as reliability, accuracy, precision, usability, and comfort is not available. The aim of the present study was to develop a low-cost bite force measurement device allowing for subject-specific customization, comfortable bite force expression, and reliable force estimation over time. The device was realized using an inexpensive load cell, two 3D printed ergonomic forks hosting reusable subject-specific silicone molds, a read-out system based on a low-cost microcontroller, and a wireless link to a personal computer. A simple model was used to estimate bite force taking into account individual morphology and device placement in the mouth. Measurement reliability, accuracy, and precision were assessed on a calibration dataset. A validation procedure on healthy participants was performed to assess the repeatability of the measurements over multiple repetitions and sessions. A 2% precision and 2% accuracy were achieved on measurements of forces in the physiological range of adult bite forces. Multiple recordings on healthy participants demonstrated good repeatability (coefficient of variation 11%) with no significant effect of repetition and session. The novel device provides an affordable and reliable solution for assessing maximum bite force that can be easily used to perform clinical evaluations in single sessions or in longitudinal studies. 相似文献
45.
46.
Eleonora Loi Cesare Zavattari Alessandro Tommasi Loredana Moi Matteo Canale Agnese Po Claudia Sabato Ana Florencia Vega-Benedetti Pina Ziranu Marco Puzzoni Eleonora Lai Luca Faloppi María Rulln Juan Carrascosa Irene Amat Jesús M. Urman Maria Arechederra Carmen Berasain Elisabetta Ferretti Andrea Casadei-Gardini Matías A. Avila Sergio Alonso Mario Scartozzi Patrizia Zavattari 《British journal of cancer》2022,126(12):1783
Background Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices.Subject terms: Diagnostic markers, Biliary tract cancer 相似文献
47.
Francesco Landi Riccardo Calvani Matteo Tosato Anna Maria Martone Domenico Fusco Alex Sisto Elena Ortolani Giulia Savera Sara Salini Emanuele Marzetti 《Journal of the American Medical Directors Association》2017,18(1):88.e17-88.e24
Objectives
Declining muscle mass and function are hallmarks of the aging process. The preservation of muscle trophism may protect against various negative health outcomes. Age- and sex-specific curves of muscle mass, strength, and function, using data from a large sample of community-dwelling people, are necessary.Material and methods
Two surveys (Longevity Check-up and Very Important Protein [VIP]), conducted during EXPO 2015 in Milan, consisted of a population assessment aimed at evaluating the prevalence of specific health metrics in subjects outside of a research setting (n = 3206), with a special focus on muscle mass, strength, and function. Muscle mass was estimated by using mid-arm muscle circumference (MAMC) and calf circumference of the dominant side. Muscle strength and function were assessed through handgrip strength testing and repeated chair stand test, respectively.Results
The mean age of 3206 participants in the Longevity Check-up and VIP surveys was 51.9 years (SD 15.6, range 18–98 years), and 1694 (52.8%) were women. Cross-sectional inspection suggests that both calf circumference and MAMC decline nonlinearly with age and the rate of decline varies by gender. These measures are stable until 50 years and then begin to decrease slightly with age, with the effect being more evident in men than in women. The main effect of the age category was observed in muscle strength and physical performance parameters. Muscle strength declined significantly after 45 years of age, both in men and women (P < .001). The muscle quality of the upper extremities, defined as handgrip strength divided by MAMC, declined significantly with aging, as well (P < .001). The time to complete the chair stand test was similar from 18 years to 40 to 44 years, and then a linear decline in performing the test across age groups was observed, with an increased time of more than 3 seconds, both in men and women (P < .001).Conclusions
Muscle mass and strength curves may be used to extract reference values for subsequent use in research as well as in the clinical setting. In particular, the analyses of trajectories of muscle parameters may help identify cutoffs for the estimation of risk of adverse events. 相似文献48.
Roberto Lorusso Samuel Heuts Federica Jiritano Roberto Scrofani Carlo Antona Guglielmo Actis Dato Paolo Centofanti Sandro Ferrarese Matteo Matteucci Antonio Miceli Mattia Glauber Enrico Vizzardi Sandro Sponga Igor Vendramin Andrea Garatti Carlo de Vincentis Michele De Bonis Silvia Ajello Giovanni Troise Margherita Dalla Tomba Filiberto Serraino 《Interactive Cardiovascular and Thoracic Surgery》2022,35(1)
Open in a separate window OBJECTIVESAlthough the intra-aortic balloon pump (IABP) has been the most widely adopted temporary mechanical support device in cardiac surgical patients, its use has declined. The current study aimed to evaluate the occurrence and predictors of early mortality and complication rates in contemporary cardiac surgery patients supported by an IABP.METHODSA multicentre, retrospective analysis was performed of all consecutive cardiac surgical patients receiving perioperative balloon pump support in 8 centres between January 2010 to December 2019. The primary outcome was early mortality, and secondary outcomes were balloon-associated complications. A multivariable binary logistic regression model was applied to evaluate predictors of the primary outcome.RESULTSThe study cohort consisted of 2615 consecutive patients. The median age was 68 years [25th percentile 61, 75th percentile 75 years], with the majority being male (76.9%), and a mean calculated 30-day mortality risk of 10.0%. Early mortality was 12.7% (n = 333), due to cardiac causes (n = 266), neurological causes (=22), balloon-related causes (n = 5) and other causes (n = 40). A composite end point of all vascular complications occurred in 7.2% of patients, and leg ischaemia was observed in 1.3% of patients. The most important predictors of early mortality were peripheral vascular disease [odds ratio (OR) 1.63], postoperative dialysis requirement (OR 10.40) and vascular complications (OR 2.57).CONCLUSIONSThe use of the perioperative IABP proved to be safe and demonstrated relatively low complication rates, particularly for leg ischaemia. As such, we believe that specialists should not be held back to use this widely available treatment in high-risk cardiac surgical patients when indicated. 相似文献
49.
50.
Lara Ahmad Pietro Businaro Simone Regalbuto Matteo Gastaldi Elisabetta Zardini Marta Panzeri Elisa Vegezzi Giuseppe Fiamingo Elena Colombo Sabrina Ravaglia 《Medicine》2022,101(30)
Single reports of Guillain-Barré syndrome (GBS) have been reported worldwide during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. While case reports are likely to be biased toward uncommon clinical presentations, systematic assessment of prospective series can highlight the true clinical features and spectrum. In this prospective, observational study, we included all consecutive patients who developed GBS. In patients with SARS-CoV-2 infection as antecedent, the time-gap between the infection and GBS onset had to be ≤30 days. The referral was a neurological University Research Hospital, in the Italian Region more severely involved by the pandemic, and hospitalizing both COVID+ and non-COVID neurological diseases. Clinical, laboratory, cerebrospinal fluid, and electromyographic features of GBS diagnosed between March 2020 and March 2021 were compared to a retrospective series of GBS diagnosed between February 2019 and February 2020 (control population). Nasopharyngeal swab was still positive at GBS onset in 50% of patients. Mild-to-moderate COVID-related pneumonia, as assessed by X-ray (6 patients) or X-ray plus computerized tomography (2 patients) co-occurred in 6 of 10 patients. GBS diagnosed during the pandemic period, including 10 COVID-GBS and 10 non–COVID-GBS, had higher disability on admission (P = .032) compared to the GBS diagnosed between February 2019 and 2020, possibly related to later hospital referral in the pandemic context. Compared to non–COVID-GBS (n = 10) prospectively diagnosed in the same period (March 2020–2021), post–COVID-GBS (n = 10) had a higher disability score on admission (P = .028), lower sum Medical Research Council score (P = .022) and lymphopenia (P = .025), while there were no differences in GBS subtype/variant, severity of peripheral involvement, prognosis and response to treatment. Cerebrospinal fluid search for SARS-CoV-2 RNA and antiganglioside antibodies were negative in all COVID+ patients. Temporal clustering of cases, coinciding with the waves of the pandemic, and concomitant reduction of the incidence of COVID-negative GBSs may indicate a role for SARS-CoV-2 infection in the development of GBS, although the association may simply be related to a bystander effect of systemic inflammation; lack of prevalence of specific GBS subtypes in post–COVID-GBS also support this view. GBS features and prognosis are not substantially different compared to non–COVID-GBS. 相似文献