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1.
Phys Rev Lett ; 120(23): 232502, 2018 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-29932707

RESUMEN

We report the result of the search for neutrinoless double beta decay of ^{82}Se obtained with CUPID-0, the first large array of scintillating Zn^{82}Se cryogenic calorimeters implementing particle identification. We observe no signal in a 1.83 kg yr ^{82}Se exposure, and we set the most stringent lower limit on the 0νßß ^{82}Se half-life T_{1/2}^{0ν}>2.4×10^{24} yr (90% credible interval), which corresponds to an effective Majorana neutrino mass m_{ßß}<(376-770) meV depending on the nuclear matrix element calculations. The heat-light readout provides a powerful tool for the rejection of α particles and allows us to suppress the background in the region of interest down to (3.6_{-1.4}^{+1.9})×10^{-3} counts/(keV kg yr), an unprecedented level for this technique.

2.
Biochim Biophys Acta Mol Basis Dis ; 1863(9): 2182-2191, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28572004

RESUMEN

Dystroglycan (DG) serves as an adhesion complex linking the actin cytoskeleton to the extracellular matrix. DG is encoded by a single gene as a precursor, which is constitutively cleaved to form the α- and ß-DG subunits. α-DG is a peripheral protein characterized by an extensive glycosylation that is essential to bind laminin and other extracellular matrix proteins, while ß-DG binds the cytoskeleton proteins. The functional properties of DG depend on the correct glycosylation of α-DG and on the cross-talk between the two subunits. A reduction of α-DG glycosylation has been observed in muscular dystrophy and cancer while the inhibition of the interaction between α- and ß-DG is associated to aberrant post-translational processing of the complex. Here we used confocal microscopy based techniques to get insights into the influence of α-DG glycosylation on the functional properties of the ß-DG, and its effects on cell migration. We used epithelial cells transfected with wild-type and with a mutated DG harboring the mutation T190M that has been recently associated to dystroglycanopathy. We found that α-DG hypoglycosylation, together with an increased protein instability, reduces the membrane dynamics of the ß-subunit and its clustering within the actin-rich domains, influencing cell migration and spontaneous cell movement. These results contribute to give novel insights into the involvement of aberrant glycosylation of DG in the developing of muscular dystrophy and tumor metastasis.


Asunto(s)
Movimiento Celular , Distroglicanos/metabolismo , Seudópodos/metabolismo , Animales , Línea Celular , Distroglicanos/genética , Glicosilación , Ratones , Microscopía Confocal , Estabilidad Proteica , Seudópodos/genética
3.
Br J Cancer ; 112(10): 1675-86, 2015 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-25880005

RESUMEN

BACKGROUND: Despite the recognised contribution of the stroma to breast cancer development and progression, the effective targeting of the tumor microenvironment remains a challenge to be addressed. We previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells. This study was designed to better define the role played, especially by CAFs, in promoting breast tumor cell migration. METHODS: Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of NFs and CAFs on gene and protein expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), in MCF-7 and MDA-MB-231 cells. To assess the role of SREBP1 in the regulation of SCD1 expression, the desaturase levels were also determined in tumor cells treated with an SREBP1 inhibitor. Migration was evaluated by wound-healing assay in SCD1-inhibited (by small-interfering RNA (siRNA) or pharmacologically) cancer cells and the effect of CAF-conditioned medium was also assessed. To define the role of stroma-derived signals in cancer cell migration speed, cell-tracking analysis was performed in the presence of neutralising antibodies to hepatocyte growth factor, transforming growth factor-ß or basic fibroblast growth factor. RESULTS: A two to three fold increase in SCD1 mRNA and protein expression has been induced, particularly by CAFs, in the two cancer cell lines that appear to be dependent on SREBP1 activity in MCF-7 but not in MDA-MB-231 cells. Both siRNA-mediated and pharmacological inhibition of SCD1 impaired tumor cells migration, also when promoted by CAF-released soluble factors. Fibroblast-triggered increase in cancer cell migration speed was markedly reduced or abolished by neutralising the above growth factors. CONCLUSION: These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies.


Asunto(s)
Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Movimiento Celular/genética , Fibroblastos/patología , Comunicación Paracrina/genética , Estearoil-CoA Desaturasa/genética , Neoplasias de la Mama/genética , Diferenciación Celular/genética , Línea Celular Tumoral , Membrana Celular/genética , Técnicas de Cocultivo/métodos , Transición Epitelial-Mesenquimal/genética , Femenino , Factores de Crecimiento de Fibroblastos/genética , Factor de Crecimiento de Hepatocito/genética , Humanos , Células MCF-7 , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Factor de Crecimiento Transformador beta/genética
4.
Soft Matter ; 11(28): 5719-26, 2015 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-26083581

RESUMEN

SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.


Asunto(s)
Neoplasias Colorrectales/ultraestructura , Citoesqueleto/ultraestructura , Ganglios Linfáticos/ultraestructura , Invasividad Neoplásica/ultraestructura , Línea Celular Tumoral , Forma de la Célula , Neoplasias Colorrectales/química , Neoplasias Colorrectales/patología , Citoesqueleto/química , Humanos , Ganglios Linfáticos/química , Metástasis Linfática/patología , Metástasis Linfática/ultraestructura , Fenómenos Mecánicos , Microscopía de Fuerza Atómica , Invasividad Neoplásica/patología , Propiedades de Superficie
5.
APL Bioeng ; 8(1): 016115, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38435469

RESUMEN

The pressing need for multifunctional materials in medical settings encompasses a wide array of scenarios, necessitating specific tissue functionalities. A critical challenge is the occurrence of biofouling, particularly by contamination in surgical environments, a common cause of scaffolds impairment. Beyond the imperative to avoid infections, it is also essential to integrate scaffolds with living cells to allow for tissue regeneration, mediated by cell attachment. Here, we focus on the development of a versatile material for medical applications, driven by the diverse time-definite events after scaffold implantation. We investigate the potential of incorporating graphene oxide (GO) into polycaprolactone (PCL) and create a composite for 3D printing a scaffold with time-controlled antibacterial and anti-adhesive growth properties. Indeed, the as-produced PCL-GO scaffold displays a local hydrophobic effect, which is translated into a limitation of biological entities-attachment, including a diminished adhesion of bacteriophages and a reduction of E. coli and S. aureus adhesion of ∼81% and ∼69%, respectively. Moreover, the ability to 3D print PCL-GO scaffolds with different heights enables control over cell distribution and attachment, a feature that can be also exploited for cellular confinement, i.e., for microfluidics or wound healing applications. With time, the surface wettability increases, and the scaffold can be populated by cells. Finally, the presence of GO allows for the use of infrared light for the sterilization of scaffolds and the disruption of any bacteria cell that might adhere to the more hydrophilic surface. Overall, our results showcase the potential of PCL-GO as a versatile material for medical applications.

6.
Nanotechnology ; 24(49): 495302, 2013 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-24231603

RESUMEN

In this paper we present a simple and robust method to realize highly ordered arrays of stretched and suspended DNA molecules over the millimeter length scale. To this end we used an ad hoc designed superhydrophobic surface made of high aspect-ratio silicon pillars, where we deposited a droplet containing genomic DNA. A precise positioning of DNA strands was achieved by shaping the silicon pillars so that sharpened features resembling tips were included. Such features allowed us to accurately control the droplet de-wetting dynamics, pinning DNA strands in a well-defined position above pillars. The proposed technique has the potential to positively impact on the development of novel DNA chips for genetic analysis.


Asunto(s)
ADN/análisis , Nanoestructuras/química , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Propiedades de Superficie , Sangre/metabolismo , Diseño de Equipo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Nanotecnología , Humectabilidad
7.
J Sports Med Phys Fitness ; 53(5): 520-3, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23903532

RESUMEN

Ventricular repolarization abnormalities (VRA) in athletes with apparently normal hearts, have always represented a challenging problem for sports physicians. We describe the case of an athlete with giant negative T waves and ST segment depression on resting electrocardiogram (ECG), "small" left ventricular cavity size and mild segmental hypertrophy at the echocardiogram (ECHO). After only 2 months of detraining, ECHO features were almost identical but ECG abnormalities disappeared. He has been followed in our Outpatient Clinic for 17 years, during which he had some cardiovascular complications, strongly suggestive of Hypertrophic Cardiomyopathy. At last stress test ECG, moreover, reappearance of VRA at high workloads and during the recovery period was documented. In conclusion, even if marked VRA disappear after a detraining period, we believe that they always represent a mark of an underlying disease and not just a sign of athlete's heart.


Asunto(s)
Arritmias Cardíacas/fisiopatología , Atletas , Cardiomegalia Inducida por el Ejercicio/fisiología , Electrocardiografía , Prueba de Esfuerzo/efectos adversos , Recuperación de la Función , Descanso/fisiología , Adolescente , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiología , Diagnóstico Diferencial , Humanos , Masculino
8.
Clin Exp Allergy ; 42(11): 1643-53, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23106665

RESUMEN

BACKGROUND: Specific food-dependent exercise-induced anaphylaxis (S-FDEIAn) is a distinct form of food allergy in which symptoms are elicited by exercise performed after ingesting food to which the patient has become sensitised. Non-specific FDEIAn (NS-FDEIAn) is a syndrome provoked by exercise performed after ingesting any food. OBJECTIVE: We sought to identify the culprit allergenic molecules in patients with FDEIAn, combining 'classic' allergy testing with an allergenic molecule-based microarray approach for IgE detection. METHODS: All subjects were evaluated who reported at least one episode of anaphylaxis in association with physical exercise performed within 4 h after a meal. We performed skin prick tests (SPT) with commercial food extracts, prick plus prick tests (P + P) with fresh foods (P + P), and serum specific IgE assays by means of both the ImmunoCAP (CAP) and the ISAC 89 microarray system (ISAC). RESULTS: Among our 82 FDEIAn patients, the most frequent suspected foods were tomato, cereals, and peanut. SPT, P + P, and CAP displayed different degrees of sensitivity. Each test disclosed some positivities not discovered by others. Seventy-nine subjects were positive to at least one food (49 to more than 20), whereas three were negative. All suspected foods were positive to at least one of SPT, P + P, and CAP. When tested using the ISAC, 64 (78%) subjects were positive to Pru p 3 [peach lipid transfer protein (LTP)], 13 were positive to other food allergen molecules, and five displayed negative results to all food allergenic molecules. Overall, 79 patients probably had S-FDEIAn and the other 3 NS-FDEIAn. CONCLUSIONS: Multiple food hypersensitivity represents a clinical hallmark of a large percentage of FDEIAn patients. The very high prevalence of IgE to the LTP suggests a role of this allergen group in causing S-FDEIAn.


Asunto(s)
Anafilaxia/etnología , Anafilaxia/etiología , Proteínas Portadoras/inmunología , Ejercicio Físico , Hipersensibilidad a los Alimentos/etnología , Hipersensibilidad a los Alimentos/etiología , Población Blanca , Adolescente , Adulto , Alérgenos/inmunología , Anafilaxia/diagnóstico , Niño , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Italia , Masculino , Persona de Mediana Edad , Pruebas Cutáneas , Adulto Joven
9.
Pathog Glob Health ; 116(5): 297-304, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35138229

RESUMEN

The early administration of anti-SARS-CoV-2 monoclonal antibodies (mAb) could decrease the risk of severe disease and the need of inpatients care. Herein, our clinical experience with Bamlanivimab/Etesevimab for the treatment of early SARS-CoV-2 infection through an outpatient service was described. Patients with confirmed COVID-19 were selected by General Practitioners (GPs) if eligible to mAb administration, according to manufacturer and AIFA (Agenzia-Italiana-del-Farmaco) criteria. If suitability was confirmed by the Multidisciplinary Team, the patient was evaluated within the next 48-72 hours. Then, all patients underwent a medical evaluation, followed by mAb infusion or hospitalization if the medical condition had worsened. Overall, from March 29th to June 4th, 2021, 106 patients with confirmed COVID-19 were identified by GPs; 26 were considered not eligible and then excluded, while 9 refused treatment. Among the 71 remaining, 6 were not treated because of worsening of symptoms soon after selection. Finally, 65 received mAb therapy. All treated patients survived. However, 2/65 developed adverse events (allergic reaction and atrial fibrillation, respectively) and 6/65 needed hospitalization. By performing univariate logistic regression analysis, diabetes was the only risk factor for hospitalization after mAb administration [aOR = 9.34, 95%CI = 1.31-66.49, p= .026]. Importantly, subjects who worsened awaiting mAb were more frequently obese (OR = 16.66, 95%CI = 1.80-153.9, p= .013) and received home corticosteroid therapy for COVID-19 (OR = 14.11, 95%CI = 1.53-129.6, p= .019). Establishing a network among GPs and COVID units could be an effective strategy to provide mAb treatment to patients with early SARS-CoV-2 infection to reduce hospitalizations and pressure on healthcare systems.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Humanos , Pacientes Ambulatorios , SARS-CoV-2
10.
Environ Sci Pollut Res Int ; 29(29): 44404-44412, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35133597

RESUMEN

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Linfopenia , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Exposición a Riesgos Ambientales/análisis , Mortalidad Hospitalaria , Humanos , Inmunidad , Linfopenia/inducido químicamente , Dióxido de Nitrógeno/análisis , Material Particulado/análisis , SARS-CoV-2
11.
Br J Sports Med ; 45(7): 563-70, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19696035

RESUMEN

OBJECTIVE: To collect medical data on women's boxing. DESIGN: Cross-sectional and longitudinal study. SETTING: Medical examinations requested by Italian laws. PARTICIPANTS: A retrospective study was conducted on all female boxing competitions in Italy from April 2001 to December 2007. Sixty-one amateur female boxers were evaluated longitudinally. INTERVENTIONS: (1) Retrospective study: All pre-/postmatch medical reports were analysed. (2) Prospective study: Breast, gynaecologic, brain, eyes, ear, nose and throat examinations were carried out. MAIN OUTCOME MEASUREMENTS: (1) Retrospective study: Any injury assessed before/after the match. (2) Prospective study: Health problems which could be related to boxing activity. RESULTS: (1) Retrospective study: Data from 5600 examinations were collected. Precompetition, a medical problem was recorded in three athletes (one conjunctiva hyperemia, one zygomatic bruise, one eyelid haematoma). Post competition, 51/2800 medical checks showed mild common injuries, such as soft tissue facial lesions, epistaxis and hand-wrist problems. Only one concussion was recorded with hospitalisation (for a thorough evaluation). Another athlete was hospitalised for a nasal fracture. (2) Prospective study: Two fibroadenomas, three ovarian cysts and one intramural uterine myoma were diagnosed. In four boxers, non-specific electroencephalographic abnormalities were detected, however, with a normal brain MRI in three (the fourth is still waiting for the radiologic procedure). Nasal septum deviation was common (42.6%) and a transmissive hypoacusia was observed in two athletes. No major eye injuries were reported. CONCLUSIONS: Female boxing seems to be a safe sport with a very low incidence of events requiring hospitalisation. No specific diseases in female boxers could be observed, in particular regarding the breast and reproductive system.


Asunto(s)
Boxeo/lesiones , Adulto , Traumatismos en Atletas/epidemiología , Boxeo/estadística & datos numéricos , Métodos Epidemiológicos , Femenino , Humanos , Italia/epidemiología , Examen Físico , Adulto Joven
12.
J Sports Med Phys Fitness ; 51(2): 194-203, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21681152

RESUMEN

AIM: Dancesport is increasing its popularity and it becomes to be considered as a real sport. Few studies are available about the physiological strain of dancesport competitions: moreover, recent changes in the official rules make it mandatory to revise our knowledge about the specific physiologic demands during competition. The aim of our study was to evaluate physiological parameters in top-level dancers. METHODS: Twelve competitive dancesport couples (12 Latin-American and 12 Standard dancers) composed the study population. The first testing session was aimed at determining physical and physiological characteristics of athletes in laboratory; the second, at establishing physiological responses during simulated competition on field, involving the measurement of O(2) uptake (VO(2)), heart rate and blood lactate (BL). RESULTS: Male dancers showed a peak-VO(2) of 60.9±6.0 and 59.2±7.0 mL/kg/min for Standard and Latin-American dancers, respectively. For females, peak-VO(2) was 53.7±5.0 mL/kg/min in Standard and 52.3±5.0 mL/kg/min in Latin-American dancers. During simulated competition, male dancers reached the 75.7±10.6 and 84.2±11.2% of peak-VO(2) (P<0.05) for Standard and Latin-American sequence, respectively. For females, no difference was observed (70.8±13.8% in Latin-American and 72.5±12.8% in Standard). Peak-BL during simulated Standard competition was 6.50±2.1 and 6.91±2.6 mM in males and females, respectively, and, for Latin-American sequence, 7.95±2.1 mM in males and 6.04±2.5 mM in females. CONCLUSION: Dancesport can be defined as a sport discipline with an alternate physical activity with medium lasting and high energy-demanding (both aerobic and anaerobic) consecutive phases, separated by short recovery periods. These data must be kept into account while planning specific training programs in sportdancers.


Asunto(s)
Baile/fisiología , Frecuencia Cardíaca/fisiología , Ácido Láctico/sangre , Consumo de Oxígeno/fisiología , Adulto , Femenino , Humanos , Masculino , Adulto Joven
13.
J Sports Med Phys Fitness ; 51(2): 292-8, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21681165

RESUMEN

AIM: The aim of the study was to compare baseline cognitive performance of female in respect to male amateur boxers. METHODS: Study population included 28 female amateur boxers. Fifty-six male boxers, matched for age, employment and competitive level to female athletes, formed the control group. All boxers had no history of head concussions (except boxing). Each boxer was requested to: 1) fulfill a questionnaire collecting demographic data, level of education, occupational status, boxing record and number of head concussions during boxing; 2) undergo a baseline computerized neuropsychological (NP) test (CogSport) measuring simple and complex reaction times (RT). RESULTS: Female were lighter than male boxers (56±7 vs. 73.1±9.8 kg, P<0.0001). No significant differences at CogSport scores were observed between groups. Male boxers showed a longer simple-RT at the end of the NP battery than at the beginning (0.247±0.007 vs. 0.243±0.007 s, P=0.02), however, with a significant lower rate of mistakes (0.7±1.6 vs. 2.0±3.1%, P=0.005), observed also in the female group (0.5±1.1 vs. 2.2±3.0%, P=0.005). No boxing activity parameter (record, number of knock-outs, etc.) correlated with NP scores. CONCLUSION: Female and male Olympic-style boxers have no (or minimal) differences in baseline cognitive performance. Further research with larger series of female boxers is required to confirm these findings.


Asunto(s)
Boxeo/fisiología , Pruebas Neuropsicológicas , Tiempo de Reacción/fisiología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino
14.
Nano Today ; 33: 100883, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32382315

RESUMEN

The pneumonia outbreak of coronavirus disease 2019 (COVID-19) represents a global issue. The bidimensional material graphene has captured much attention due to promising antimicrobial applications and has also demonstrated antiviral efficacy. In response to this global outbreak, we summarized the current state of knowledge of graphene and virus interaction as well as possible successful applications to fight COVID-19. Antibody-conjugated graphene sheets can rapidly detect targeted virus proteins and can be useful for large population screening, but also for the development of environmental sensors and filters, given the low cost of graphene materials. Functionalized graphene has demonstrated a good viral capture capacity that, combined with heat or light-mediated inactivation, could be used as a disinfectant. Graphene sensors arrays can be implemented on standard utility textiles and drug efficacy screening. Thanks to its high versatility, we foresee that graphene may have a leading role in the fight against COVID-19.

15.
Nutr Metab Cardiovasc Dis ; 19(4): 234-40, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19157818

RESUMEN

BACKGROUND AND AIM: To evaluate the prevalence of subclinical cardiovascular (CV) abnormalities in systemic lupus erythematosus (SLE) stratified according to SLE-related organ damage using the Systemic Lupus International Collaborating Clinics (SLICC) damage index. METHODS AND RESULTS: We selected SLE patients without clinically overt CV events (n=45, 56% with SLICC=0, 44% with SLICC=1-4). CV evaluation was performed using cardiac and vascular echo-Doppler techniques. Post-ischemic flow-mediated dilation (FMD) over nitroglycerine-mediated dilation (NMD) of the brachial artery <0.70 defined endothelial dysfunction. The prevalence of preclinical CV abnormalities (CVAbn, including at least one of the following-carotid atherosclerosis, left ventricular (LV) hypertrophy, low arterial compliance, LV wall motion abnormalities, aortic regurgitation, FMD/NMD<0.70)-was 64% (16/25) in patients with SLICC=0 and 80% (16/20) in those with SLICC>0 (p=not significant (NS)). In particular, the prevalence of carotid atherosclerosis (28% vs. 16%), of LV hypertrophy (12% vs. 6%) and of LV wall motion abnormalities (15% vs. 12%), of low global arterial compliance (18% vs. 10%), prevalence of aortic regurgitation (30% vs. 18%) and/or aortic valve fibrosclerosis (10% vs. 8%), FMD<10% (14+/-5% vs. 14%+/-6) and prevalence of FMD/NMD<0.70 (53% vs. 52%) were comparable in SLE patients with SLICC>0 and in those with SLICC=0 (all p=NS). Of the SLE patients without carotid atherosclerosis, LV hypertrophy, low arterial compliance, LV wall motion abnormalities and aortic regurgitation (n=17), endothelial dysfunction was detected in 50% of those with SLICC=0 (6/12) and in 40% of those with SLICC>0 (2/5, p=NS). CONCLUSIONS: SLE patients with SLICC=0 often have an elevated CV risk profile due to subclinical manifestations of CV disease detectable by cardiac and vascular echo-Doppler evaluations.


Asunto(s)
Arteria Braquial/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Endotelio Vascular/fisiopatología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Vasodilatación , Adolescente , Adulto , Insuficiencia de la Válvula Aórtica/epidemiología , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/fisiopatología , Arteria Braquial/diagnóstico por imagen , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/fisiopatología , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/etiología , Enfermedades de las Arterias Carótidas/fisiopatología , Adaptabilidad , Ecocardiografía Doppler en Color , Endotelio Vascular/diagnóstico por imagen , Femenino , Humanos , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Nitroglicerina , Prevalencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler , Vasodilatadores , Disfunción Ventricular Izquierda/epidemiología , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Adulto Joven
16.
J Endocrinol Invest ; 32(11): 908-12, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19609105

RESUMEN

INTRODUCTION: Eighty-six adult patients with GH deficiency (GHD) of adult or childhood onset were treated for 6 months, with recombinant human growth hormone (rhGH) at a low (LD) or conventional dose (CD). The treatment effect on insulin levels was investigated. METHODS: This manuscript refers to the Italian addendum to an International Study (B9R-EW-GDED) in which patients with GHD were randomized to receive r-hGH replacement therapy at a dose of either 3 microg/kg/day or 6 microg/kg/day for the 3 months. The dose was then doubled for the next 3 months. RESULTS: After 6 months of r-hGH treatment, insulin levels increased with both GH dosages, with a greater increase achieved in the low-dose subgroup. Insulin levels also increased significantly in the childhood-onset, while even decreased in the adult-onset subgroup. On the whole, in more than 50% of patients, insulin values rose by >13%. Moreover, mean levels of IGF-I increased 2-3 fold (p<0.001 vs baseline) in both the LD and CD groups. Significant and similar increases in IGF binding protein-3 levels were seen in both the LD and CD groups over the treatment period, regardless the time of onset of GHD. CONCLUSION: Insulin increased with both GH dosages and more than half of patients presented an important increase in insulin plasma levels. It would be of interest to assess if there is a correlation between the changes in insulin levels and other cardiovascular risk factors such as hemostatic parameters.


Asunto(s)
Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Insulina/sangre , Adulto , Femenino , Hormona de Crecimiento Humana/administración & dosificación , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Proteínas Recombinantes/uso terapéutico
17.
Nanoscale Horiz ; 4(2): 273-290, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-32254085

RESUMEN

Graphene oxide is the hot topic in biomedical and pharmaceutical research of the current decade. However, its complex interactions with human blood components complicate the transition from the promising in vitro results to clinical settings. Even though graphene oxide is made with the same atoms as our organs, tissues and cells, its bi-dimensional nature causes unique interactions with blood proteins and biological membranes and can lead to severe effects like thrombogenicity and immune cell activation. In this review, we will describe the journey of graphene oxide after injection into the bloodstream, from the initial interactions with plasma proteins to the formation of the "biomolecular corona", and biodistribution. We will consider the link between the chemical properties of graphene oxide (and its functionalized/reduced derivatives), protein binding and in vivo response. We will also summarize data on biodistribution and toxicity in view of the current knowledge of the influence of the biomolecular corona on these processes. Our aim is to shed light on the unsolved problems regarding the graphene oxide corona to build the groundwork for the future development of drug delivery technology.


Asunto(s)
Proteínas Sanguíneas/metabolismo , Grafito/sangre , Adsorción , Animales , Línea Celular Tumoral , Eritrocitos/efectos de los fármacos , Grafito/química , Grafito/metabolismo , Grafito/farmacocinética , Humanos , Macrófagos/efectos de los fármacos , Nanotubos/química , Unión Proteica
18.
J Mech Behav Biomed Mater ; 100: 103377, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31398692

RESUMEN

The umbilical cord is a complex structure containing three vessels, one straight vein and two coiled arteries, encased by the Wharton Jelly (WJ) a spongy structure made of collagen and hydrated macromolecules. Fetal blood reaches the placenta through the arteries and flows back to the fetus through the vein. The role of the WJ in maintaining cord circulation proficiency and the ultimate reason for arterial coiling still lack of reasonable mechanistic interpretations. We performed biaxial tension tests and evidenced significant differences in the mechanical properties of the core and peripheral WJ. The core region, located between the arteries and the vein, resulted rather stiffer close to the fetus. Finite element modelling and optimization based inverse method were used to create 2D and 3D models of the cord and to simulate stress distribution in different hemodynamic conditions, compressive loads and arterial coiling. We recorded a facilitated stress transmission from the arteries to the vein through the soft core of periplacental WJ. This condition generates a pressure gradient that boosts the venous backflow circulation towards the fetus. Peripheral WJ allows arteries to act as pressure buffering chambers during the cardiac diastole and helps to dissipate compressive forces away from vessels. Altered WJ biomechanics may represent the structural basis of cord vulnerability in many high-risk clinical conditions.


Asunto(s)
Fenómenos Biomecánicos , Fuerza Compresiva , Cordón Umbilical/fisiología , Gelatina de Wharton/fisiología , Adulto , Algoritmos , Anisotropía , Colágeno/fisiología , Elasticidad , Femenino , Análisis de Elementos Finitos , Análisis de Fourier , Hemodinámica , Humanos , Imagenología Tridimensional , Sustancias Macromoleculares , Placenta/fisiología , Embarazo , Presión , Estrés Mecánico , Resistencia a la Tracción , Adulto Joven
20.
Interface Focus ; 8(3): 20170059, 2018 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-29696091

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for serious hospital infections worldwide and represents a global public health problem. Curcumin, the major constituent of turmeric, is effective against MRSA but only at cytotoxic concentrations or in combination with antibiotics. The major issue in curcumin-based therapies is the poor solubility of this hydrophobic compound and the cytotoxicity at high doses. In this paper, we describe the efficacy of a composite nanoparticle made of curcumin (CU) and graphene oxide (GO), hereafter GOCU, in MRSA infection treatment. GO is a nanomaterial with a large surface area and high drug-loading capacity. GO has also antibacterial properties due mainly to a mechanical cutting of the bacterial membranes. For this physical mechanism of action, microorganisms are unlikely to develop resistance against this nanomaterial. In this work, we report the capacity of GO to support and stabilize curcumin molecules in a water environment and we demonstrate the efficacy of GOCU against MRSA at a concentration below 2 µg ml-1. Further, GOCU displays low toxicity on fibroblasts cells and avoids haemolysis of red blood cells. Our results indicate that GOCU is a promising nanomaterial against antibiotic-resistant MRSA.

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