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1.
Int J Cardiol ; 371: 10-15, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36181950

RESUMO

BACKGROUND: Well-developed collaterals are assumed as a marker of viability and ischemia in chronic total occlusions (CTO). We aim to correlate viability and ischemia with collateral presence and extent in CTO patients by cardiac magnetic resonance (CMR). METHODS: Multicentre study of 150 CTO patients undergoing stress-CMR, including adenosine if normal systolic function, high-dose-dobutamine for patients with akinetic/>2 hypokinetic segments and EF ≥35%, otherwise low-dose-dobutamine (LDD); all patients underwent late gadolinium enhancement (LGE) imaging. Viability was defined as mean LGE transmurality ≤50% for adenosine, as functional improvement for dobutamine-stress-test, ischemia as ≥1.5 segments with perfusion defects outside the scar zone. RESULTS: Rentrop 3/CC 2 defined well-developed (WD, n = 74) vs poorly-developed collaterals (PD, n = 76). Viability was equally prevalent in WD vs PD: normo-functional myocardium with ≤50% LGE in 52% vs 58% segments, p = 0.76, functional improvement by LDD in 48% vs 52%, p = 0.12. Segments with none, 1-25%,26-50%,51-75% LGE showed viability by LDD in 90%,84%,81%,61% of cases, whilst in 12% if 76-100% LGE (p < 0.01). There was no difference in WD vs PD for ischemia presence (74% vs 75%, p = 0.99) and extent (2.7 vs 2.8 segments, p = 0.77). CONCLUSIONS: In a large cohort of CTO patients, presence and extent of collaterals did not predict viability and ischemia by stress-CMR. Scar extent up to 75% LGE was still associated with viability, whereas ischemia was undetectable in 25% of patients, suggesting that the assessment of CTO patients with CMR would lead to a more comprehensive evaluation of viability and ischemia to guide revascularization.


Assuntos
Meios de Contraste , Isquemia Miocárdica , Humanos , Gadolínio , Miocárdio/patologia , Dobutamina , Adenosina , Isquemia/patologia , Valor Preditivo dos Testes , Imagem Cinética por Ressonância Magnética/métodos , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/patologia
2.
Sci Adv ; 5(8): eaau9309, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31453319

RESUMO

Malignant brain neoplasms have a poor prognosis despite aggressive treatments. Animal models and evidence from human bodily tumors reveal that sustained reduction in tumor perfusion via electrical stimulation promotes tumor necrosis, therefore possibly representing a therapeutic option for patients with brain tumors. Here, we demonstrate that transcranial electrical stimulation (tES) allows to safely and noninvasively reduce intratumoral perfusion in humans. Selected patients with glioblastoma or metastasis underwent tES, while perfusion was assessed using magnetic resonance imaging. Multichannel tES was applied according to personalized biophysical modeling, to maximize the induced electrical field over the solid tumor mass. All patients completed the study and tolerated the procedure without adverse effects, with tES selectively reducing the perfusion of the solid tumor. Results potentially open the door to noninvasive therapeutic interventions in brain tumors based on stand-alone tES or its combination with other available therapies.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Idoso , Antineoplásicos/uso terapêutico , Circulação Cerebrovascular/fisiologia , Terapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
3.
Int J Cardiol ; 272: 356-362, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30173921

RESUMO

BACKGROUND: It is debated whether percutaneous revascularization (PCI) of total coronary chronic occlusion (CTO) is superior to optimal medical therapy (OMT) in improving symptoms, left ventricular (LV) function and major adverse cardiac/cerebrovascular events (MACCE). Furthermore, CTO-PCI is a challenging technique, with lower success rate than in other settings. A systematic analysis of baseline LV function, infarction extent and ischaemic burden to predict response to revascularization has never been performed. PURPOSES: To establish a CMR protocol to identify patients (pts) who can benefit most from CTO-PCI. Myocardial viability/ischaemia retains high biological plausibility as predictors of response to revascularization. Therefore, baseline viability (necrotic tissue extent, response to inotropic stimulation) and ischaemia (perfusion defect, wall motion abnormality during stress) will be studied as potential predictors of mechanical LV segmental improvement and ischaemic burden reduction in CTO territory (primary endpoint), LV remodelling and global function, Seattle Angina Questionnaire, and MACCE improvement (secondary endpoints) in the follow-up. METHODS: Pts with CTO suitable for PCI undergo stress-CMR for viability/ischaemia assessment. Pts with normal LV function undergo adenosine, those with moderately-reduced ejection fraction (EF) and wall motion abnormalities high-dose dobutamine, pts with EF <35% low-dose dobutamine. All pts undergo late gadolinium enhancement and repeat the same scan at 12 ±â€¯3 months, regardless of PCI success or decision for OMT. CONCLUSIONS: A multi-parameter CMR protocol tailored on pts characteristics to study viability/ischaemia could help in identifying responders in terms of LV function, ischaemic burden and clinical outcome among pts suitable for CTO-PCI, improving selection of best candidates to percutaneous revascularization.


Assuntos
Oclusão Coronária/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Isquemia Miocárdica/diagnóstico por imagem , Revascularização Miocárdica/métodos , Seleção de Pacientes , Doença Crônica , Oclusão Coronária/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética/normas , Masculino , Isquemia Miocárdica/cirurgia , Revascularização Miocárdica/normas , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/normas , Estudos Prospectivos , Resultado do Tratamento
4.
J Clin Transl Endocrinol ; 7: 47-53, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29067250

RESUMO

BACKGROUND: Although hyperglycemia is a strong predictor of postoperative infective complications (PIC), little is known about the effect of basal insulin therapy (BIT) per se on PIC. AIM: To evaluate if there is an association between BIT, independent of glucose levels, and a possible improvement of PIC during the perioperative cardiosurgery period (PCP). METHODS: In 812 patients admitted for cardiac intervention and treated with a continuous intravenous insulin infusion (CIII) for hyperglycemic levels (>130 mg/dl), a retrospective analysis was performed during the PCP (January 2009-December 2011). Upon transfer to the cardiac surgery division, if fasting glucose was ≥130 mg/dl, a basal + premeal insulin therapy was initiated (121 patients, group 1); for <130 mg/dl, a premeal insulin alone was initiated (691 patients, group 2). FINDINGS: Compared with group 2, group 1 showed reductions in PIC (2.48% vs 7.96%, p < 0.049; odds ratio: 0.294; 95% CI: 0.110-0.780), C-Reactive Protein (p < 0.05) and white blood cell (p < 0.05) levels despite glucose levels and CIII that were higher during the first two days after surgery (179.8 ± 25.3 vs 169.5 ± 10.6 mg/dl, p < 0.01; 0.046 ± 0.008 vs 0.037 ± 0.015 U/kg/h, p < 0.05, respectively). Normal glucose levels were achieved in both groups from day 3 before the discharge. The mean length of hospital duration was 18% lower in group 1 than in group 2 (7.21 ± 05.08 vs 8.76 ± 9.08 days, p < 0.007), providing a significant impact on public health costs. CONCLUSIONS: Basal + preprandial insulin therapy was associated with a lower frequency of PIC than preprandial insulin therapy alone, suggesting a beneficial effect of basal insulin therapy on post-surgery outcome.

5.
Radiol Med ; 121(5): 378-90, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26909515

RESUMO

Liver transplantation has become an established curative treatment in adult patients with acute or chronic end-stage liver diseases. In pediatric cases the number of cadaveric donor livers is not sufficient and to overcome the shortage of appropriate-sized whole liver grafts, technical variants of liver transplantation have been practiced. Reduced-size cadaveric and split cadaveric allografts have become an important therapeutic option, expanding the availability of size-appropriate organs for pediatric recipients with terminal liver disease. The number of pediatric deaths awaiting liver transplantation has been reduced by the introduction of living-related liver transplantation, developed to overcome the shortage of suitable grafts for children. It is important for radiologists to know that children have distinct imaging of liver transplantation that distinguish them from adults. A multidisciplinary pediatric liver transplantation team should be skilled in pediatric conditions and in associated processes, risks and complications. Radiologists should know the common pediatric liver diseases that lead to liver transplantation, the anastomotic techniques and the expected postoperative imaging findings. The aim of this study is to illustrate the role of non-invasive imaging such us ultrasonography, color Doppler ultrasonography, multidetector computed tomography and magnetic resonance imaging in the evaluation of pediatric liver transplantation and in potential liver donors.


Assuntos
Hepatopatias/diagnóstico , Transplante de Fígado , Imageamento por Ressonância Magnética , Tomografia Computadorizada Multidetectores , Ultrassonografia Doppler em Cores , Aloenxertos , Atresia Biliar/diagnóstico , Cadáver , Criança , Doença Crônica , Humanos , Neoplasias Hepáticas/diagnóstico , Transplante de Fígado/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Ultrassonografia Doppler em Cores/métodos
6.
Clin Endocrinol (Oxf) ; 83(5): 656-62, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26201937

RESUMO

OBJECTIVE: The aim of this study was to evaluate the metabolic effects of fatty pancreas (nonalcoholic fatty pancreas disease - NAFPD) in a group of obese paediatric patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We included 121 consecutive children with echographic evidence of hepatic steatosis. All patients underwent to abdominal ultrasound to evaluate pancreatic echogenic pattern. We divided the patients into two groups on the basis of the presence of fatty pancreas. In all patients liver function tests, lipid and gluco-insulinemic profile were evaluated. A selected subset of patients (67) underwent to liver biopsy. RESULTS: Of these 121 patients, 58 showed NAFPD and 63 patients exhibited a normal pancreatic echogenic pattern. No differences were found in age, transaminases serum levels, lipid profile and pancreatic enzymes between the two groups. The patients with NAFPD had a significantly higher z-BMI, fasting insulin, insulin resistance (HOMA-IR) and lower ISI respect to the group without fatty pancreas. The patients with fatty pancreas showed a more advanced form of liver disease, with higher values of fibrosis, ballooning and NAS score with respect to the group without NAFPD. CONCLUSIONS: Our study demonstrated that NAFPD is a frequent condition in obese paediatric patients affected by NAFLD. Our data suggest that pancreatic fat should not be considered an inert accumulation of fat, but as an additional factor able to affect glucose metabolism and severity of liver disease, increasing the risk of develop metabolic syndrome.


Assuntos
Hepatopatia Gordurosa não Alcoólica/epidemiologia , Pancreatopatias/epidemiologia , Adiposidade , Adolescente , Antropometria , Biópsia , Citocinas/sangue , Feminino , Humanos , Itália/epidemiologia , Fígado/patologia , Masculino , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Pancreatopatias/sangue , Pancreatopatias/diagnóstico , Pancreatopatias/etiologia
7.
Pediatr Transplant ; 19(5): 517-26, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26059061

RESUMO

UNLABELLED: Controversy remains about the best line of division for liver splitting, through Segment IV or through the umbilical fissure. Both techniques are currently used, with the choice varying between surgical teams in the absence of an evidence-based choice. We conducted a single-center retrospective analysis of 47 left split liver grafts that were procured with two different division techniques: "classical" (N = 28, Group A) or through the umbilical fissure and plate (N = 19, Group B). The allocation of recipients to each group was at random; a single transplant team performed all transplantations. Demographics, characteristics, technical aspects, and outcomes were similar in both groups. The grafts in Group A, prepared with the classical technique, were procured more often with a single BD orifice compared with the grafts in Group B; however, this was not associated with a higher incidence of biliary problems in this series of transplants (96% actual graft survival rate [median ± s.d. FOLLOW-UP: 26 ± 20 months]). Both techniques provide good quality split grafts and an excellent outcome; surgical expertise with a given technique is more relevant than the technique itself. The classical technique, however, seems to be more flexible in various ways, and surgeons may find it to be preferable.


Assuntos
Hepatectomia/métodos , Transplante de Fígado/métodos , Fígado/cirurgia , Procedimentos Cirúrgicos Operatórios , Adulto , Criança , Pré-Escolar , Bases de Dados Factuais , Sobrevivência de Enxerto , Humanos , Lactente , Doadores Vivos , Pessoa de Meia-Idade , Estudos Retrospectivos , Obtenção de Tecidos e Órgãos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Umbigo/cirurgia
8.
Pediatr Obes ; 9(5): e99-e102, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24302697

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) may develop from non-alcoholic fatty liver disease (NAFLD) either in the presence or in the absence of established cirrhosis. Non-cirrhotic patients with NAFLD-related HCC are usually adult, male and obese. However, this association has not been reported yet in younger age groups. Objectives In the present study, the clinical case of a 7-yaer-old obese boy with steatosis and HCC is presented. METHODS: A 7-year-old boy, with no evidence of chronic liver disease, was admitted for assessment of a liver mass. Preliminary assessment was suggestive of a combined and severe liver steatosis together with a malignant disease. RESULTS: A biopsy confirmed the suspected diagnosis of HCC; interestingly, the non-neoplastic liver was surrounded and characterized by the presence of steatosis and ballooning, and being absent of lobular inflammation and fibrosis. Chemotherapy and diet changes were conducted successfully with ultrasound characteristics suggesting improvements on both aspects: conventional liver mass resection could take place. CONCLUSIONS: This case report suggests that HCC might develop in paediatric age patients with obesity-related NAFLD, even in the absence of fibrosis.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fígado/patologia , Obesidade Infantil/complicações , Redução de Peso , Biópsia , Índice de Massa Corporal , Carcinoma Hepatocelular/terapia , Criança , Comorbidade , Humanos , Neoplasias Hepáticas/terapia , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade Infantil/patologia , Obesidade Infantil/terapia , Resultado do Tratamento
9.
J Pediatr Surg ; 48(5): 1006-11, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23701774

RESUMO

BACKGROUND: Strictures of the extra-hepatic biliary tree are rare in children and have a benign non-traumatic inflammatory origin or are related to idiopathic fibrosing pancreatitis. Primary sclerosing cholangitis (PSC) can manifest as multiple biliary strictures or as a single dominant stricture. We describe the presentation, treatment, and outcome of six cases of isolated benign choledochal stricture (IBCS). METHODS: All patients underwent magnetic resonance cholangiography (MRC). Five patients underwent diagnostic and therapeutic ERCP, and 4 patients underwent intra-choledochal mini-probe EUS and biopsy. Colonoscopy was performed in suspected ulcerative colitis (UC). RESULTS: We report 6 patients (mean age at diagnosis: four males, 12.1 years; two females, 14.2 years) with IBCS. Clinical onset included 3 cases of acute biliary pancreatitis and obstructive jaundice, one obstructive jaundice, one cholestasis, and one pancreatitis. At diagnosis, MRC confirmed IBCS in all patients. Biliary sphincterotomy, stricture dilation, and stenting were performed in 4 patients. One child underwent hepaticojejunostomy for a type I choledocal cyst. During follow-up (mean: 21 months; range: 1-3 years), all patients were asymptomatic. Four patients developed UC (three pancolitis, one descending colitis). One child developed PSC. CONCLUSION: IBCS can be successfully treated by therapeutic ERCP. The occurrence of UC could suggest that IBCS is a form of PSC.


Assuntos
Colangite Esclerosante/diagnóstico , Ducto Colédoco/patologia , Imageamento por Ressonância Magnética , Adolescente , Criança , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/diagnóstico por imagem , Cisto do Colédoco/complicações , Cisto do Colédoco/diagnóstico por imagem , Colestase Extra-Hepática/complicações , Colite Ulcerativa/complicações , Colonoscopia , Ducto Colédoco/diagnóstico por imagem , Constrição Patológica/diagnóstico , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Constrição Patológica/patologia , Dilatação , Endossonografia , Feminino , Seguimentos , Humanos , Icterícia Obstrutiva/etiologia , Masculino , Pancreatite/complicações , Esfinterotomia Endoscópica , Stents
10.
Pediatr Surg Int ; 29(6): 659-62, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23417547

RESUMO

Rhabdomyosarcoma is the most common tumor of the biliary tract in children. Although some features at preoperative radiographic studies (ultrasound, CT, MRI) may be suggestive of BT-RMS, until few years ago the final diagnosis was obtained by either operative or transcutaneous biopsy, thus exposing to a risk of regional dissemination. More recent and still anecdotal, is the histological diagnosis on tissue obtained by transluminal biopsy either during transhepatic cholangiography or endoscopic retrograde cholangio-pancreatography (ERCP), the latter having the major advantage of a much lower risk of loco-regional dissemination. We present two cases of BT-RMS that were histologically diagnosed by intracholedocal biopsy performed during ERCP, after being suspected at conventional imaging.


Assuntos
Biópsia/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Neoplasias do Ducto Colédoco/diagnóstico , Ducto Colédoco/patologia , Rabdomiossarcoma/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
11.
Radiol Med ; 117(8): 1408-18, 2012 Dec.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-22986694

RESUMO

PURPOSE: Cystic-fibrosis-associated liver disease (CFLD) may lead to portal hypertension (PHT) and cirrhosis. Clinical signs and biochemistry of liver involvement are not discriminating. The aim of the study was to evaluate the performance of acoustic radiation force impulse (ARFI) with virtual tissue quantification in comparison with clinical signs, biochemistry and standard hepatic ultrasound (US) patterns. MATERIALS AND METHODS: Virtual Touch Tissue Quantification, an implementation of US ARFI with shear-wave velocity (SWV) measurements was used in 75 children with cystic fibrosis (CF) and suspected CFLD to quantify hepatic stiffness. In each patient, ten measurements of SWV were performed on the right hepatic lobe. Patients were also evaluated by standard diagnostic tools (standard US, liver- and lung function tests, oesophagogastroscopy). RESULTS: Among CF patients, median SWV was significantly higher in patients with clinical, biochemical and US signs of hepatic involvement than in patients without US evidence of liver disease 1.08 m/s [(95% confidence interval (CI), 1.02-1.14]. Median SWV values in patients with portal hypertension, splenomegaly and oesophageal varices were 1.30 (95% CI, 1.17-1.43), 1.54 (95% CI, 1.32-1.75) and 1.63 (95% CI, 1.26-1.99), respectively. Differences were significant (p<0.001). CONCLUSIONS: ARFI is an innovative screening technique able to help identify CFLD in children.


Assuntos
Fibrose Cística/complicações , Técnicas de Imagem por Elasticidade , Hepatopatias/diagnóstico por imagem , Adolescente , Varizes Esofágicas e Gástricas/complicações , Feminino , Humanos , Hipertensão Portal/complicações , Fígado/diagnóstico por imagem , Hepatopatias/complicações , Masculino , Esplenomegalia/complicações , Esplenomegalia/diagnóstico por imagem
12.
Nutr Metab Cardiovasc Dis ; 22(1): 58-65, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20709514

RESUMO

BACKGROUND AND AIMS: The relationship between atrial natriuretic peptide (ANP), increased free fatty acid (FFA) and insulin resistance in patients with mitral valve disease (MVD), a group characterised by elevated atrial pressure and increased ANP levels, is not defined. The present study was performed to evaluate, in MVD patients, the relationship between increased ANP and FFA levels and insulin resistance and the role of mitral valve replacement/repair in ameliorating these metabolic alterations. Conversely, coronary heart disease (CHD) patients were evaluated before and after coronary artery bypass grafting (CABG), since they are known to be insulin resistant in the presence of chronic FFA increase. METHODS AND RESULTS: Fifty MVD patients and 55 CHD patients were studied before and 2 months after surgery and compared with 166 normal subjects. Before surgery, 56% of MVD patients had impaired glucose tolerance or newly diagnosed type 2 diabetes after a standard oral glucose load and this percentage decreased to 46% after surgery. In CHD, impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetic patients were 67% of patients before and after CABG. In MVD, left atrial (LA) volume, ANP, FFA incremental area and insulin levels were higher and Insulin Sensitivity (IS) index significantly reduced while after surgery, LA volume, ANP and FFA significantly decreased and IS index significantly improved. In CHD, insulin resistance and hyperinsulinaemia were present both before and after surgery with increased tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels. CONCLUSION: In MVD, a higher degree of abnormal glucose tolerance and insulin resistance are associated to increased levels of ANP and FFA, while these metabolic alterations are improved by mitral valve replacement/repair surgery. Clinical Trial.gov registration number NCT 00520962.


Assuntos
Fator Natriurético Atrial/sangue , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/sangue , Doenças das Valvas Cardíacas/cirurgia , Resistência à Insulina , Idoso , Ponte de Artéria Coronária , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Intolerância à Glucose/metabolismo , Humanos , Interleucina-6/análise , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Valva Mitral/patologia , Análise de Regressão , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
13.
Pediatr Transplant ; 16(7): E265-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22093884

RESUMO

FNH is a rare and benign tumor of the liver. It is not a conventional indication for liver transplantation, and no transplant for FNH in a child has been reported to date. Multifocal FNH growing in adolescent age to a widespread tumor invading the whole liver and associated with severe refractory pruritus was an unusual indication for transplantation in a 13-yr-old girl. The operation and the follow-up were uneventful, allowing full recovery and disappearance of pruritus.


Assuntos
Hiperplasia Nodular Focal do Fígado/complicações , Hiperplasia Nodular Focal do Fígado/terapia , Transplante de Fígado/métodos , Prurido/terapia , Adolescente , Criança , Feminino , Humanos , Fígado/anormalidades , Fígado/patologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
15.
Nutr Metab Cardiovasc Dis ; 21(7): 512-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20227256

RESUMO

BACKGROUND AND AIMS: The number of Endothelial Progenitor Cells (EPCs) is considered a novel marker of cardiovascular (CV) disease. It is not clear which are the main determinants of EPC number in apparently healthy subjects in the absence of overt clinical CV or metabolic abnormalities. We evaluated the main clinical determinants of EPC levels in a population of healthy subjects with normal glucose tolerance. METHODS AND RESULTS: EPC number was determined in 122 healthy subjects (73M/49F;36.6 ± 8yrs). Blood samples were collected to test biochemical variables. OGTT was performed and insulin resistance/compensatory hyperinsulinemia was defined according to fasting plasma insulin (FPI) levels. EPCs were identified as cells co-expressing CD133/CD34/KDR antigens by flow-cytometry. CD133(+)/KDR(+) count inversely correlated with BMI (rho=-0.18;p < 0.05), waist circumference (-0.2;<0.05), diastolic (-0.23;<0.01) and systolic blood pressure (-0.21;<0.05), uric acid (-0.24;<0.005), PAI-1 (-0.197; <0.05) and FPI (-0.2;<0.05) and directly correlated with HDL cholesterol (0.182;<0.05). CD34(+)/CD133(+)/KDR(+) count inversely correlated with uric acid (-0.28;<0.005) and FPI (-0.2;<0.05). EPC number was lower in males (p < 0.05) and gender was the only independent predictor of EPC count (p < 0.05). By dividing the population in four subgroups based on gender and insulin resistance, CD133(+)/KDR(+) levels were lower in insulin resistant compared to insulin sensitive males (p < 0.05) with no differences in females. CONCLUSION: The male gender is an independent predictor of low EPC levels in healthy subjects. This might contribute to explaining the higher CV risk in males compared to pre-menopausal age-matched females. In this study a reduced EPC number seems to be associated with insulin resistance in male subjects.


Assuntos
Células Endoteliais/citologia , Hiperinsulinismo/sangue , Resistência à Insulina , Células-Tronco/citologia , Antígeno AC133 , Adulto , Antígenos CD/metabolismo , Antígenos CD34/metabolismo , Biomarcadores , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Contagem de Células , Estudos Transversais , Células Endoteliais/metabolismo , Feminino , Glicoproteínas/metabolismo , Humanos , Hiperinsulinismo/fisiopatologia , Itália/epidemiologia , Masculino , Peptídeos/metabolismo , Fatores Sexuais , Células-Tronco/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
Diabetologia ; 54(2): 433-9, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21046356

RESUMO

AIMS/HYPOTHESIS: Type 1 diabetes is considered non-reversible at end-stage disease when there is no measurable insulin production. However, there are indications that insulin-producing beta cells could be present or return if autoimmunity could be controlled. We therefore sought to determine whether immunosuppression therapy can reinstate beta cell function in patients with long-term type 1 diabetes. METHODS: We examined pancreatic beta cell function in 22 patients with long-term type 1 diabetes (median disease duration 27 years), who had been receiving rapamycin monotherapy (0.1 mg/kg; target trough levels 8-10 ng/ml; 26-314 days) as pre-conditioning for islet transplantation. As control, beta cell function was measured in 14 patients (median disease duration 17 years) who were waiting for an islet transplant without rapamycin pre-conditioning. RESULTS: Fasting C-peptide increased from <0.03 nmol/l (0.0066 nmol/l, interquartile range [IQR] 0.0003-0.023) at baseline to 0.039 nmol/l (IQR 0.0066-0.096) at end of rapamycin monotherapy (p < 0.005). In 12 patients, fasting C-peptide increased to >0.076 nmol/l (C-peptide responders). Exogenous insulin requirement decreased from 0.64 U/kg daily (IQR 0.56-0.72) to 0.57 U/kg (IQR 0.45-0.70; p = 0.01), but this reduction was significant only in the 12C-peptide-responsive patients. Rapamycin monotherapy was also associated with a decrease in insulin antibody titre (median decrease 110 to 35.9 U/ml; p < 0.001) and fasting serum proinsulin (median decrease 0.51 to 0.28 pmol/l; p = 0.001). All variables remained unchanged in the 14 control patients. CONCLUSIONS/INTERPRETATION: Therapies to reinstate beta cell function may be applicable to patients with long-term C-peptide-negative type 1 diabetes. TRIAL REGISTRATION: ClinicalTrial.gov NCT01060605.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/fisiopatologia , Imunossupressores/uso terapêutico , Células Secretoras de Insulina/fisiologia , Sirolimo/uso terapêutico , Adulto , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proinsulina/sangue
17.
Eur J Clin Nutr ; 63(10): 1220-5, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19536163

RESUMO

BACKGROUND AND OBJECTIVES: A cross-sectional observation suggests that total antioxidant capacity (TAC) of the diet positively affects plasma concentrations of beta-carotene independent of beta-carotene intake. This study was carried out to investigate the effect of two dietary strategies, designed to be comparable in fruits, vegetables, fibre, alcohol and beta-carotene intake but substantially different in their TAC, on changes in antioxidant intake and antioxidant status, and in particular in circulating beta-carotene concentrations. SUBJECTS: A randomized cross-over intervention trial involving 33 healthy participants and consisting of two 14-day dietary periods (high TAC diet, HT; low TAC diet, LT) with a 14-day washout in between was conducted. RESULTS: Energy, macronutrient, dietary fibre, alcohol and beta-carotene intake was not significantly different between LT and HT, whereas intake of other carotenoids and dietary TAC was significantly higher in the HT than in the LT (P<0.001). Circulating carotenoids (with the exception of alpha-carotene, which followed an inverse trend) and alpha-tocopherol decreased significantly during the LT and increased during the HT period. Among these, beta-carotene almost doubled its concentration in plasma after the HT diet. CONCLUSIONS: The increase in circulating beta-carotene along with the increase in dietary TAC suggests that plasma beta-carotene could be a marker of TAC intake rather than of beta-carotene intake itself. This may explain, in part, why beta-carotene supplementation alone has shown no benefit in chronic disease prevention and adds to a putative beneficial role of high dietary TAC diets, which merits further investigation.


Assuntos
Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Inflamação/sangue , beta Caroteno/administração & dosagem , beta Caroteno/sangue , Consumo de Bebidas Alcoólicas , Biomarcadores/sangue , Estudos Cross-Over , Fibras na Dieta/administração & dosagem , Feminino , Sequestradores de Radicais Livres , Frutas , Humanos , Inflamação/epidemiologia , Inflamação/prevenção & controle , Hepatopatias/sangue , Hepatopatias/epidemiologia , Hepatopatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Verduras , Vitaminas/administração & dosagem , Vitaminas/sangue
18.
J Neurol Neurosurg Psychiatry ; 76(7): 960-4, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15965202

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has remained poorly understood. Tumour necrosis factor alpha (TNFalpha), which has been implicated in the pathogenesis of ADC, is predominantly localised in macrophages in the HIV infected brain, although in vitro studies indicate that neurones can express this cytokine. OBJECTIVE: To examine the clinical/neuroradiological features of HIVL and the expression of TNFalpha in HIVL. METHODS: Six patients who presented with rapidly progressive dementia within four to 12 weeks of the primary manifestation of their HIV infection were evaluated. Clinical history, treatment regimens, and imaging studies were reviewed, and brain samples from three of the patients were studied by means of immunohistochemistry. RESULTS: Imaging studies showed diffuse bilateral deep white matter changes in all six patients. Clinical and imaging abnormalities improved in five of the six patients within weeks after initiation of antiretroviral treatment. Brain biopsies of two showed pronounced microglia/macrophage activation, but only scant viral protein (gp41) expression. Staining for TNFalpha was found in microglia/macrophages, and surprisingly, in neurones also. Postmortem analysis of a third patient also showed TNFalpha expression in neurones of the frontal cortex and basal ganglia. CONCLUSION: This study provides the first demonstration of staining for TNFalpha in the neurones of the HIV infected brain, and suggests that the process underlying this rapidly progressive form of ADC may reflect indirect mechanisms mediated by host factors, particularly TNFalpha.


Assuntos
Complexo AIDS Demência/patologia , Encéfalo/patologia , Fator de Necrose Tumoral alfa/análise , Complexo AIDS Demência/diagnóstico , Complexo AIDS Demência/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Gânglios da Base/patologia , Biópsia , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Seguimentos , Lobo Frontal/patologia , Proteína gp41 do Envelope de HIV/análise , Humanos , Macrófagos/patologia , Masculino , Microglia/patologia , Pessoa de Meia-Idade , Exame Neurológico , Neurônios/patologia , Testes Neuropsicológicos , Saquinavir/administração & dosagem , Estavudina/administração & dosagem , Resultado do Tratamento , Zidovudina/administração & dosagem
19.
Genome ; 47(4): 633-8, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15284867

RESUMO

The objectives of this study were to assess the genetic variability of haploids (2n = 2x = 24) extracted from tetraploid Solanum tuberosum through 4x x 2x crosses with Solanum phureja. Molecular and phenotypic analyses were performed to fingerprint the genotypes used and to evaluate their potential use in breeding programs. AFLP analysis revealed the presence of specific bands derived from the tetraploid seed parent S. phureja, as well as ex novo originated bands. On average, 210 bands were visualized per genotype, 149 (70%) of which were common to both parental genotypes. The percentage of S. tuberosum specific bands ranged from 25.1% to 18.6%, with an average of 22%. The fraction of genome coming from S. phureja ranged from 1.9% to 6.5%, with an average value of 4%. The percentage of ex novo bands varied from 1.9% to 9.0%. The presence of S. phureja DNA is very interesting because it indicated that S. phureja pollinator is involved in the mechanism of haploid formation. The characterization for resistance to Erwinia carotovora subsp. carotovora and potato virus X (PVX) provided evidence that haploids may express traits that are lacking in the tetraploids they come from, which can be useful for both genetic studies and breeding purposes. It is noteworthy that genotypes combining resistance to both diseases and good pollen stainability were identified. Other possible breeding implications owing to the presence of S. phureja genome in the haploids analyzed are discussed.


Assuntos
Solanum tuberosum/genética , Cruzamento , Cruzamentos Genéticos , Variação Genética , Genoma de Planta , Haploidia , Hibridização Genética , Pectobacterium carotovorum/patogenicidade , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Poliploidia , Potexvirus/patogenicidade , Solanum tuberosum/microbiologia , Solanum tuberosum/virologia
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