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1.
BMC Infect Dis ; 23(1): 718, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37875792

RESUMEN

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.


Asunto(s)
COVID-19 , Tromboembolia Venosa , Humanos , Anticoagulantes/efectos adversos , COVID-19/complicaciones , Enoxaparina/efectos adversos , Hemorragia/tratamiento farmacológico , Heparina/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
2.
Extremophiles ; 22(5): 769-780, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30047030

RESUMEN

Eukaryotic eIF5A and its bacterial orthologue EF-P are translation elongation factors whose task is to rescue ribosomes from stalling during the synthesis of proteins bearing particular sequences such as polyproline stretches. Both proteins are characterized by unique post-translational modifications, hypusination and lysinylation, respectively, which are essential for their function. An orthologue is present in all Archaea but its function is poorly understood. Here, we show that aIF5A of the crenarchaeum Sulfolobus solfataricus is hypusinated and forms a stable complex with deoxyhypusine synthase, the first enzyme of the hypusination pathway. The recombinant enzyme is able to modify its substrate in vitro resulting in deoxyhypusinated aIF5A. Moreover, with the aim to identify the enzyme involved in the second modification step, i.e. hypusination, a set of proteins interacting with aIF5A was identified.


Asunto(s)
Proteínas Arqueales/metabolismo , Factores de Iniciación de Péptidos/metabolismo , Procesamiento Proteico-Postraduccional , Sulfolobus solfataricus/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo
3.
Radiol Med ; 118(5): 752-98, 2013 Aug.
Artículo en Italiano | MEDLINE | ID: mdl-23184241

RESUMEN

Cardiac magnetic resonance (CMR) is considered an useful method in the evaluation of many cardiac disorders. Based on our experience and available literature, we wrote a document as a guiding tool in the clinical use of CMR. Synthetically we describe different cardiac disorders and express for each one a classification, I to IV, depending on the significance of diagnostic information expected.


Asunto(s)
Enfermedades Cardiovasculares/diagnóstico , Imagen por Resonancia Magnética/métodos , Medios de Contraste , Humanos , Italia
4.
Radiol Med ; 117(8): 1333-46, 2012 Dec.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-23090256

RESUMEN

PURPOSE: The aim of this study was to assess the feasibility of low-dose computed tomography (CT) with the adaptive statistical iterative reconstruction (ASIR) algorithm in whole-body imaging with low tube voltage and current. MATERIALS AND METHODS: Twenty-three patients underwent whole-body CT with 40% of ASIR and parameters modulated according to body mass index (BMI). All had previously undergone conventional-dose CT with 100% filtered back projection (FBP). Two radiologists jointly assessed image quality (sharpness, noise, artefacts) and diagnostic quality blinded to the scanning technique. The effective dose and image quality obtained with the ASIR protocol were compared with those obtained with the FBP algorithm. RESULTS: The mean effective dose achieved with ASIR was 15.6 ± 5 mSv versus 21.8 ± 5.3 mSv with the FBP protocol (p<0.0001). Image quality was good in all low-dose CT scans, and diagnostic quality was comparable with or superior to that of conventional-dose CT. CONCLUSIONS: Low-dose CT with the ASIR algorithm is feasible and ensures significant reduction in effective dose.


Asunto(s)
Algoritmos , Procesamiento de Imagen Asistido por Computador , Dosis de Radiación , Tomografía Computarizada por Rayos X , Imagen de Cuerpo Entero , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intensificación de Imagen Radiográfica , Adulto Joven
5.
Radiol Med ; 117(6): 901-38, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22466874

RESUMEN

Cardiac computed tomography (CCT) has grown as a useful means in different clinical contexts. Technological development has progressively extended the indications for CCT while reducing the required radiation dose. Even today there is little documentation from the main international scientific societies describing the proper use and clinical indications of CCT; in particular, there are no complete guidelines. This document reflects the position of the Working Group of the Cardiac Radiology Section of the Italian Society of Radiology concerning the indications for CCT.


Asunto(s)
Enfermedades Cardiovasculares/diagnóstico por imagen , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Humanos , Italia , Dosis de Radiación , Tomografía Computarizada por Rayos X/instrumentación , Tomografía Computarizada por Rayos X/métodos
6.
Clin Ter ; 173(6): 528-533, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36373450

RESUMEN

Purpose: Globally, age and some comorbidities have been associ-ated with the risk of more severe outcomes of COVID-19. The purpose of this research is to calculate the hospitalization rate of SARS-CoV-2 positive patients in an Italian Local health Authority (LHA) and to examine whether medical comorbidities encoded through pharmaceutical administrative data are predictors of hospital admission in patients with a positive SARS-CoV-2 naso-pharyngeal swab. Methods: This retrospective observational study was conducted in a LHA of Pescara. Comorbidities were coded through the consumption of drugs, using the WHO's Anatomical Therapeutic Chemical (ATC) classification System. The admission was ascertained by checking the hospital discharge records where generated. Results: During the study period, 1571 patients were tested positive for SARS-CoV-2 oro-and-nasopharyngeal swab. Multivariable logistic analisys showed as predictors of admission an age ≥65 in the total sample (aOR 10.91; 95%CI 6.86-17.36) as well as in the male (aOR 12.64;95%CI 6.42-24.87) and female. (aOR 9.27; 95%CI 4.87-17.66) in SARS-CoV-2 positive patients. Comorbidities assiociated with admission were (GERD) in overall (AdjOR 1.58; 95% CI 1.06-2.34) and male (AdjOR 2.30; 95%CI 1.12-4.72) samples and anticoagulants drugs use in male (AdjOR 3.90; 95% 1.11-13.65) sample, the presence of congestive heart failure (CHF) in female (AdjOR 0.47;95%CI 0.27-0.83) sample results as protective factor. Conclusion: In conclusion, increasing age, male gender and PPI use are positively associated while female gender and CHF-related drug use are negatively associated with hospitalization in SARS-CoV-2 positive patients.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Masculino , Femenino , COVID-19/epidemiología , COVID-19/terapia , Hospitalización , Comorbilidad , Hospitales
7.
J Cardiovasc Surg (Torino) ; 52(3): 429-35, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21577196

RESUMEN

AIM: Aim of our study was to evaluate multidetector 64-slice spiral computed tomography (MSCT) as an alternative to traditional coronary angiography (CA) to detect concomitant coronary artery disease (CAD) in patients initially admitted for non-coronary surgical procedures. METHODS: We have analyzed data of 380 consecutive patients operated from 2006 to 2008 initially admitted for aortic (N.=170) or mitral (N.=67) valve disease, ascending aorta aneurysm ± aortic valve disease (N.=99), and other (combined valve diseases, tumors; N.=44). These patients were submitted either to MSCT (Group CT, N.=112) or to CA (Group A, N.=268). Inclusion criteria to perform MSCT were no previous myocardial infarction or documented CAD, normal left ventricular function, sinus rhythm, less than 2-3 premature ventricular or atrial contractions /min. RESULTS: In Group CT, CAD was definitively excluded in 95 patients (85%) and was detected in 17; 8 of those 17 patients were subsequently submitted to CA and coronary artery bypass surgery for significant CAD. As compared to those in Group A, patients in Group CT were younger (64±15 vs. 70±10 years, P<0.0001), had less hypertension (P=0.0001), chest pain (P<0.05), peripheral vascular disease (P<0.05). NYHA class, incidence of diabetes, smoking habit, family history of CAD were similar. The incidence of operative mortality, postoperative myocardial infarction was not significantly different in both Group CT (0%) and A (0.4%) (P=NS). CONCLUSION: In selected cardiac surgical patients less invasive 64-slice MSCT can be with some limits an alternative to CA to rule out CAD, as confirmed by the absence of postoperative ischemic complications.


Asunto(s)
Angiografía/métodos , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada Espiral , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Cardíacos , Enfermedades Cardiovasculares/cirugía , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Procedimientos Quirúrgicos Vasculares
8.
Radiol Med ; 116(5): 675-89, 2011 Aug.
Artículo en Inglés, Polaco | MEDLINE | ID: mdl-21293945

RESUMEN

PURPOSE: This study retrospectively evaluated the prevalence of anatomical coronary artery variants and congenital anomalies in 3,236 patients imaged with 64-slice computed tomography (CT). MATERIALS AND METHODS: Over a period of 4 years, 3,236 patients underwent CT coronary angiography performed with the standard protocol. We assessed coronary artery dominance, presence of the intermediate branch, presence and number of diagonal and marginal branches and coronary anomalies subdivided into anomalies of origin and course, intrinsic anomalies and termination anomalies. RESULTS: Coronary dominance was right-sided in 88.1% of patients; the intermediate branch was present in 21.3%, the number of diagonal and marginal branches was one to two in >90%, and the number of coronary anomalies was 224 (89 of origin and course, 129 intrinsic anomalies and six termination anomalies). CONCLUSIONS: Sixty-four-slice CT coronary angiography provides accurate three-dimensional evaluation of the coronary artery tree with correct visualisation of any coronary anomalies, a relatively common finding that had a prevalence of 5.7% in our study population.


Asunto(s)
Angiografía Coronaria/métodos , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anomalías de los Vasos Coronarios/epidemiología , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Prevalencia , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios Retrospectivos
9.
Radiol Med ; 116(2): 163-77, 2011 Mar.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-21311993

RESUMEN

PURPOSE: The aim of our study was to evaluate the role of magnetic resonance (MR) imaging in identifying the location and extent of acute ischaemic injury to predict reversibility and distinguish areas of acute from chronic ischaemia in patients with acute coronary syndrome non- ST-elevation myocardial infarction (NSTEMI). MATERIALS AND METHODS: We evaluated 22 patients with NSTEMI acute coronary syndrome confirmed by coronary angiography (CA). We studied ventricular function indices and segmental changes in wall thickness and kinetics by cine-MR imaging sequences. Subsequently, we evaluated myocardial wall oedema with T2-weighted black-blood short-tau inversion recovery turbo spin echo (T2 BB-STIRTSE) sequences and identified areas of myocardial necrosis using T1-weighted turbo field-echo inversion recovery (T1 TFE-IR) sequences after contrast material administration. RESULTS: The results obtained with the single sequences were as follows: T2 BB-STIR-TSE: 96.8% sensitivity, 100% specificity, 99.7% negative predictive value, 99.7% positive predictive value; T1 TFE-IR: 45.8% sensitivity, 96.9% specificity, 92.3% negative predictive value, 90.3% positive predictive value; systolic wall thickening: 87.5% sensitivity, 91.8% specificity, 98.7% negative predictive value, 50% positive predictive value, 91.4% accuracy. CONCLUSIONS: Our study suggests that the sequences used for evaluating oedema and assessing viability allow for precise localisation and differentiation of areas of acute and chronic ischaemia by quantifying the possible mismatch between ischaemia and necrosis.


Asunto(s)
Síndrome Coronario Agudo/complicaciones , Imagen por Resonancia Cinemagnética/métodos , Isquemia Miocárdica/diagnóstico , Síndrome Coronario Agudo/diagnóstico por imagen , Medios de Contraste , Angiografía Coronaria , Electrocardiografía , Femenino , Gadolinio DTPA , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/etiología , Necrosis , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
10.
Radiol Med ; 115(8): 1167-78, 2010 Dec.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-20852959

RESUMEN

PURPOSE: Our aim was to evaluate the accuracy, sensitivity and specificity of 64-slice multidetector computed tomography (MDCT) in the assessment of occlusions and stenoses of arterial and venous bypass grafts and disease progression in the native vessels distal to the graft, and to compare the results with those of conventional coronary angiography. MATERIALS AND METHODS: We enrolled 78 individuals (45 men, 33 women; mean age 59) and evaluated 213 bypass grafts using a 64-slice MDCT scanner. All patients underwent conventional coronary angiography with a mean time interval between the two examinations of 2 days. RESULTS: One patient was excluded due to arrhythmia during the examination. The 212 bypass grafts in the remaining 77 patients (98.7%) consisted of 115 (54%) venous grafts and 97 (46%) arterial grafts. In the 115 venous grafts, MDCT showed a sensitivity, specificity and accuracy of 100% in evaluating occluded grafts and a sensitivity of 94.4%, specificity of 98.4% and accuracy of 96.9% in evaluating significant stenoses. In evaluating occluded arterial grafts, sensitivity was 83.3%, specificity 100% and accuracy 98.9%, whereas in evaluating stenoses of arterial grafts, sensitivity was 100%, specificity 97.7% and accuracy 98%. CONCLUSIONS: Sensitivity, specificity and accuracy in evaluating native coronary vessels distal to the graft allow for a complete assessment of the surgical and native circulation. The examination appears therefore to be exhaustive in ruling out or confirming the presence of diseased vessels in the postoperative follow-up.


Asunto(s)
Puente de Arteria Coronaria , Oclusión de Injerto Vascular/diagnóstico por imagen , Complicaciones Posoperatorias/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Angiografía Coronaria , Circulación Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad
11.
Radiol Med ; 115(3): 341-53, 2010 Apr.
Artículo en Inglés, Italiano | MEDLINE | ID: mdl-20017003

RESUMEN

PURPOSE: This study was done to evaluate the feasibility, sensitivity and specificity of 64-slice computed tomography (CT) in identifying haemodynamically significant (>50%) coronary artery stenoses in patients with suspected acute coronary syndrome (ACS) by correlating the CT findings with the clinical event and data provided by conventional coronary angiography (CCA). MATERIALS AND METHODS: Sixty-four patients (38 men and 26 women; mean age 65 years; range+/-10 years) presenting to our hospital's emergency department with a clinical suspicion of ACS were studied with 64-slice CT followed by CCA within 24 h of arrival. RESULTS: Two patients (3.1%) were excluded from the analysis due to artefacts. Per-patient analysis in the remaining 62 patients identified 24 cases (38.7%) of negative CT findings (no stenoses or stenoses <50%), 35 cases of positive CT findings (56.4%) with identification of the culprit lesion, two cases in which the culprit lesion was not identified and one patient with unconfirmed stenosis. Sensitivity and specificity were 94.6% and 96%, respectively. Per-vessel analysis (186 vessels) revealed 17 non-evaluable vessels (9.1%) due to motion artefacts, 61 vessels (32.8%) with stenosis >50%, seven overestimated vessels (3.7%) due to extensive calcifications, three vessels (1.6%) with underestimated stenosis and 98 vessels (52.6%) without stenosis. Sensitivity and specificity were 95.3% and 93.3%, respectively. CONCLUSIONS: In this type of emergency, coronary CT angiography could lead to considerably lower healthcare costs by identifying patients without coronary disease and allowing immediate discharge without any need for further diagnostic procedures.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Análisis de Varianza , Distribución de Chi-Cuadrado , Medios de Contraste , Angiografía Coronaria , Diagnóstico Diferencial , Estudios de Factibilidad , Femenino , Humanos , Yopamidol/análogos & derivados , Masculino , Persona de Mediana Edad , Interpretación de Imagen Radiográfica Asistida por Computador , Sensibilidad y Especificidad
12.
Am J Nephrol ; 29(3): 145-52, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18753739

RESUMEN

BACKGROUND: Several classical risk factors are at the base of vascular calcifications in hemodialysis patients. Among these, according to a general opinion, also bone turnover plays a role, which, however, requires a better definition. In addition, it has been suggested that there is a relationship between primary osteoporosis and vascular calcifications. This bone biopsy-based study on a hemodialysis patient cohort is a contribution to the evaluation of these alleged relations. METHODS: This study has been carried out on a cohort of 32 patients on maintenance hemodialysis, who were subjected to transiliac bone biopsy for histomorphometric, histodynamic and bone aluminum deposit evaluation. The patients were also examined with multislice computerized tomography for quantitation of heart and coronary calcifications. RESULTS: The patients were affected by renal osteodystrophy with a wide range of bone formation rate values. A significant negative correlation was found between the rate of bone turnover and log-transformed cardiac calcification score (p < 0.003). There were also negative significant correlations between the cardiac and coronary calcification score log and trabecular number (p < 0.02 and p < 0.05, respectively), while the correlations were positive with trabecular separation (p < 0.03 and p < 0.05, respectively). However, multiregression analysis, forward method, selected only age, hemodialysis age and serum Ca as predictive variables of cardiac and coronary calcification score log, while the histomorphometric and histodynamic variables were excluded. CONCLUSIONS: In this study, in spite of the suggestive findings of the univariate statistical approach, a further multivariate analysis was indicative of a spurious association between calcification scores and both bone turnover and histomorphometric parameters of trabecular mass and connectivity. Bone turnover and trabecular mass do not appear to be prominently connected with the extent of cardiac and coronary calcifications in hemodialysis patients.


Asunto(s)
Remodelación Ósea , Calcinosis/diagnóstico por imagen , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico por imagen , Diálisis Renal , Adulto , Factores de Edad , Anciano , Calcinosis/etiología , Calcio/sangre , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/etiología , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/complicaciones , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/patología , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios/patología , Femenino , Humanos , Ilion/patología , Masculino , Persona de Mediana Edad , Miocardio/patología , Osteoporosis/etiología , Osteoporosis/patología , Tomografía Computarizada por Rayos X , Uremia/complicaciones , Uremia/diagnóstico por imagen , Uremia/patología
13.
Am J Surg ; 218(6): 1128-1133, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31607386

RESUMEN

BACKGROUND: Endovascular therapy provides a less invasive alternative to open surgery for critically ill patients who have sustained arterial injuries. The purpose of this study was to evaluate recent trends in the management of arterial injuries in the United States with specific reference to the use of endovascular strategies and to examine the outcomes of endovascular vs open therapy for the treatment of civilian arterial traumatic injuries. METHODS: We performed a 10-year (2004-2014) analysis of ACS-NTDB and identified all adult trauma patients who had arterial injuries. Data regarding demographics, injury parameters, endovascular or open vascular repair and outcomes were extracted. Cochran-Armitage trend analysis and multivariate logistic regression analysis were performed. RESULTS: A total of 111,061 patients with arterial injuries were identified and included in our analysis. Mean age was 39 ± 19y, 82% were male and 79% were white. The most common artery injured was iliac artery followed by brachial artery and thoracic aorta. Overall 6.7% (7434) patients underwent endovascular repair while 38.8% (42,495) had open vascular repair. The rate of endovascular repair increased from 3.1% to 8.9% while the incidence of open vascular repair decreased from 47% to 32% over the study period. Patients in endovascular group had lower ISS compared to patients in open vascular repair group (17 + 10 vs 24 + 10, p < 0.001). Patients who underwent endovascular repair had shorter hospital length of stay (days: 10 + 17 vs 11 + 15, p < 0.001), lower mortality (8% vs 14%, p = 0.01). On multivariate regression analysis after controlling for confounding variables, endovascular repair was independently associated with improved survival (OR: 2.45[1.84-4.26], p = 0.01). CONCLUSIONS: The use of endovascular modalities to repair arterial injuries in the setting of acute trauma is increasing in a dramatic fashion. Endovascular repair of trauma arterial injuries is associated with shorter length of stay and improved survival compared to open vascular procedures.


Asunto(s)
Enfermedad Crítica , Procedimientos Endovasculares , Pautas de la Práctica en Medicina/estadística & datos numéricos , Lesiones del Sistema Vascular/cirugía , Adulto , Bases de Datos Factuales , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación/estadística & datos numéricos , Masculino , Tasa de Supervivencia , Estados Unidos , Lesiones del Sistema Vascular/mortalidad
14.
Sci Adv ; 5(5): eaau8857, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31123703

RESUMEN

Optimal autophagic activity is crucial to maintain muscle integrity, with either reduced or excessive levels leading to specific myopathies. LGMD2H is a muscle dystrophy caused by mutations in the ubiquitin ligase TRIM32, whose function in muscles remains not fully understood. Here, we show that TRIM32 is required for the induction of muscle autophagy in atrophic conditions using both in vitro and in vivo mouse models. Trim32 inhibition results in a defective autophagy response to muscle atrophy, associated with increased ROS and MuRF1 levels. The proautophagic function of TRIM32 relies on its ability to bind the autophagy proteins AMBRA1 and ULK1 and stimulate ULK1 activity via unanchored K63-linked polyubiquitin. LGMD2H-causative mutations impair TRIM32's ability to bind ULK1 and induce autophagy. Collectively, our study revealed a role for TRIM32 in the regulation of muscle autophagy in response to atrophic stimuli, uncovering a previously unidentified mechanism by which ubiquitin ligases activate autophagy regulators.


Asunto(s)
Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Autofagia , Ubiquitina-Proteína Ligasas/genética , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Línea Celular , Transdiferenciación Celular , Humanos , Lisina/metabolismo , Ratones , Ratones Noqueados , Distrofia Muscular de Cinturas/metabolismo , Distrofia Muscular de Cinturas/patología , Mioblastos/citología , Mioblastos/metabolismo , Unión Proteica , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
15.
J Nephrol ; 21(4): 603-8, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18651552

RESUMEN

BACKGROUND: Dialysis patients show a very high prevalence of cardiovascular complications, affected as they are with abnormal and accelerated vascular calcifications and, eventually, calcium and phosphorous metabolism disorders. Multislice computed tomography (MSCT) provides a reproducible, high-resolution imaging of calcium contained in cardiac arteries, measured by Agatston score. The aim of the present study was to evaluate the influence of high-dose and low-dose calcitriol therapy on the progression of cardiac vascular calcifications in dialyzed patients. METHODS: We enrolled 36 dialyzed patients in a prospective study, including an interventional period of 12 months and a follow-up period of 12 months. Eighteen protocol patients received intravenous pulses of high-doses calcitriol at the end of dialytic treatment and sevelamer hydrochloride therapy. Control patients received low-dose calcitriol and sevelamer hydrochloride as well. Two MSCT scans were performed: 1 at the start of the study and 1 at the end of follow-up, and Agatston score was calculated at both examinations. RESULTS: At first examination, protocol patients showed almost the same level of cardiac vascular calcification as control patients. At the second MSCT, statistically significantly higher values of Agatston score were recorded for all patients. Indeed, patients who showed higher baseline values developed worse calcifications as recorded at the end of follow-up, both in the protocol and control group. CONCLUSIONS: Our data show that baseline level is strongly predictive of vascular calcification progression, and, moreover, there is no association between calcitriol administered doses and the progression of cardiac vascular calcification.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Calcinosis/inducido químicamente , Calcitriol/administración & dosificación , Enfermedad Coronaria/inducido químicamente , Fallo Renal Crónico/terapia , Anciano , Conservadores de la Densidad Ósea/efectos adversos , Calcinosis/diagnóstico por imagen , Calcinosis/epidemiología , Calcitriol/efectos adversos , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/epidemiología , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Inyecciones Intravenosas , Italia/epidemiología , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X
16.
Cell Death Differ ; 13(4): 586-96, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16239931

RESUMEN

Mitochondrial Ca2+ uptake controls cellular functions as diverse as aerobic metabolism, cytosolic Ca2+signalling and mitochondrial participation in apoptosis. Modulatory inputs converging on the organelle can regulate this process, determining the final outcome of Ca2+-mediated cell stimulation. We investigated in HeLa cells and primary skeletal myotubes the effect on Ca2+ signalling of the transcriptional peroxisome-proliferator-activated-receptor-gamma-coactivator-1alpha (PGC-1alpha), which triggers organelle biogenesis and modifies the mitochondrial proteome. PGC-1alpha selectively reduced mitochondrial Ca2+ responses to cell stimulation by reducing the efficacy of mitochondrial Ca2+ uptake sites and increasing organelle volume. In turn, this affected ER Ca2+ release and cytosolic responses in HeLa cells. Most importantly, the modulation of mitochondrial Ca2+ uptake significantly reduced cellular sensitivity to the Ca2+-mediated proapoptotic effect of C2 ceramide. These results reveal a primary role of PGC-1alpha in shaping mitochondrial participation in calcium signalling, that underlies its protective role against stress and proapoptotic stimuli in pathophysiological conditions.


Asunto(s)
Apoptosis , Señalización del Calcio , Calcio/metabolismo , Proteínas de Choque Térmico/metabolismo , Mitocondrias Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Factores de Transcripción/metabolismo , Agonistas Adrenérgicos beta/farmacología , Albuterol/farmacología , Animales , Canales de Calcio/metabolismo , Inhibidores Enzimáticos/farmacología , Células HeLa , Proteínas de Choque Térmico/genética , Histamina/farmacología , Homeostasis , Humanos , Receptores de Inositol 1,4,5-Trifosfato , Canales Iónicos , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Mitocondrias Musculares/efectos de los fármacos , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Dilatación Mitocondrial , Fibras Musculares Esqueléticas/patología , Factor Nuclear 1 de Respiración/genética , Factor Nuclear 1 de Respiración/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Ratas , Receptores Citoplasmáticos y Nucleares/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacología , Factores de Transcripción/genética , Transfección , Proteína Desacopladora 2
17.
J Cardiovasc Surg (Torino) ; 48(3): 315-21, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17505436

RESUMEN

The aim of the study was to demonstrate the utility of endovascular stent-graft repair for emergency management of aorto-iliac surgery complications. Between 1997 and 2004, in our institute, 201 patients underwent transluminal endovascular graft placement. In 3 patients (1.4%), previously submitted to conventional aortic surgery, endovascular treatment was carried out due to the occurrence of late complications: 1 secondary aortocaval fistula, 1 impending rupture of aortic pseudoaneurysm and 1 secondary aorto-enteric fistula. All candidates were high surgical risk patients (ASA III-IV) suitable for endoprosthesis positioning by endovascular stent-graft implantation presenting with severe worsening conditions in an emergency situation. The patients were treated under local anesthesia and mild sedation. After treatment there was complete resolution of the clinical presentation and an improvement of general conditions in all 3 patients. In the 1(st) patient legs edema disappeared and in the 2(nd) patient mesogastric pain is absent, respectively at 30 and 8 months. The 3(rd) patient, with secondary aorto-enteric fistula, was submitted 2 months later to aortic graft removal and axillo-bifemoral bypass because of infection development. For the treatment of abdominal aortic surgery complications in high risk patients, particularly in emergency situations, endovascular approach is a feasible and safe alternative to conventional open repair. Further evaluation of this technique and longer follow-up will determine its exact role in the management of these life-threatening complications.


Asunto(s)
Aneurisma Falso/cirugía , Aneurisma de la Aorta Abdominal/cirugía , Enfermedades de la Aorta/cirugía , Fístula Arteriovenosa/cirugía , Implantación de Prótesis Vascular/métodos , Prótesis Vascular , Fístula del Sistema Digestivo/cirugía , Stents , Fístula Vascular/cirugía , Anciano , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Angiografía de Substracción Digital , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/etiología , Aortografía/métodos , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/etiología , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/instrumentación , Fístula del Sistema Digestivo/diagnóstico por imagen , Fístula del Sistema Digestivo/etiología , Servicios Médicos de Urgencia , Estudios de Factibilidad , Humanos , Masculino , Diseño de Prótesis , Radiografía Intervencional , Medición de Riesgo , Factores de Riesgo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Fístula Vascular/diagnóstico por imagen , Fístula Vascular/etiología , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/cirugía
18.
G Chir ; 28(8-9): 337-9, 2007.
Artículo en Italiano | MEDLINE | ID: mdl-17785049

RESUMEN

The Authors present three cases of axillary polymastia and examine the embryological and morphological aspects of this anomaly, including related surgical problems.


Asunto(s)
Axila/anomalías , Mama/anomalías , Adolescente , Adulto , Mama/cirugía , Femenino , Humanos
19.
Int J Biol Markers ; 21(2): 123-6, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16847815

RESUMEN

BACKGROUND: There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression. PATIENTS AND METHODS: IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia. RESULTS: Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (p<0.001) coupled with an increase in both IGFBP-1 (p=0.001) and, to a lesser extent, IGFBP-3 (p=0.5). CONCLUSIONS: The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.


Asunto(s)
Anilidas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Nitrilos/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Tamoxifeno/administración & dosificación , Triazoles/administración & dosificación , Anciano , Anciano de 80 o más Años , Anastrozol , Apoptosis , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/biosíntesis , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/biosíntesis , Masculino , Persona de Mediana Edad , Compuestos de Tosilo
20.
Circulation ; 110(20): 3234-8, 2004 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-15533862

RESUMEN

BACKGROUND: Computed tomography has been shown to be useful in the evaluation of aortocoronary bypass grafts (CABG). This is the first prospective study to evaluate the accuracy of a new-generation scanner in the detection of patency and significant stenoses (>50% decrease in diameter) of venous and arterial grafts in patients with previous CABG. METHODS AND RESULTS: In 96 patients (80 males, mean age 62 years) with previous CABG, a multislice computed tomography (MSCT) scan was performed (collimation 16x0.625 mm). Patients with atrial fibrillation, renal failure, severe respiratory disease, severe heart failure, heart rate >70 bpm despite therapy, or unstable angina were excluded. A total of 285 conduits implanted on the native coronary arteries at the time of CABG were evaluated. MSCT data were analyzed by 2 independent radiologists and compared with the results of conventional angiography. Three patients were excluded from analysis. All conduits were judged evaluable in 84 patients. Among these patients, MSCT correctly diagnosed 54 occluded grafts and 4 significant stenoses on the body of the grafts. Of the 17 significant anastomotic lesions, MSCT correctly diagnosed 15. For these 84 patients, diagnostic accuracy was 99%, sensitivity was 97%, and specificity was 100%. When all 93 patients were considered, the sensitivity of MSCT in diagnosing significant stenoses was 96%. CONCLUSIONS: MSCT with the new-generation scanner allows for accurate assessment of venous and arterial conduits in patients with previous CABG with a high degree of sensitivity and specificity. Exclusion criteria and radiation exposure remain limitations of the method.


Asunto(s)
Puente de Arteria Coronaria , Reestenosis Coronaria/diagnóstico por imagen , Oclusión de Injerto Vascular/diagnóstico por imagen , Tomografía Computarizada Espiral , Anciano , Angiografía , Arterias/trasplante , Angiografía Coronaria , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Arterias Mamarias , Persona de Mediana Edad , Flebografía , Periodo Posoperatorio , Estudios Prospectivos , Sensibilidad y Especificidad , Tomografía Computarizada Espiral/instrumentación , Venas/trasplante
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