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3.
Hipertens Riesgo Vasc ; 39(2): 62-68, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-35305932

RESUMO

INTRODUCTION: Hypertension (HTN) is the leading cause of mortality and disability in the world. In Argentina, almost 44% of hypertensives do not know about their condition and this may be due to the low rate of blood pressure (BP) measurements during the office visit. Our hypothesis is that the measurement and electronic recording of BP (BPMR) is not a routine practice in Argentina. OBJECTIVE: To describe the rate of office BP measurement in Argentina. METHODS: This is a retrospective, multicentre, point prevalence study. We analysed all office visits on 9/19/2019 at 9 medical institutions in 6 provinces of Argentina. RESULTS: Two thousand and eighty-two office visits were analysed. The patients' mean age was 52.1 years (18-103), 1790 (59.7%) were female, and 702 (36.1%) were hypertensives. BP was measured in 420 visits (14.1%; 95% CI 12.8-15.4). In a multivariate logistic regression model, history of HTN (OR 1.91, P<.001) and previous cardiovascular event (OR 1.76, P<.001) were associated with more odds of BPMR. The presence of cancer was associated with fewer odds of BPMR (OR .51, P<.01). Cardiology measured BP up to 49.5% (144/291 visits), followed by internal medicine 30% (152/507 visits). CONCLUSION: BPMR during office visits is deficient in Argentina and represents a missed healthcare opportunity. Different strategies are needed to detect hypertensive patients and reduce cardiovascular events.


Assuntos
Determinação da Pressão Arterial , Hipertensão , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos
4.
Food Chem ; 333: 127464, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32659667

RESUMO

The aim of this work was to identify and quantify the bioaccesible phenolic compounds and evaluate their relationship with the antioxidant properties of three different cookies formulated with 10.5% peach pulp incorporation and 50% fat or added-sucrose reduction. Peach pulp and dietary fiber were incorporated in cookie formulation and two levels of fat or sucrose were analyzed. Cookie quality was modified by fruit incorporation and reduction of fat and added-sucrose. Fruit incorporation changed the polyphenol profile and improved antioxidant properties. Most phenolic compounds quantified in both the extracts and the different stages of the simulated digestion were higher in the sucrose/fat reduced samples than in the control samples, which represents a nutritional improvement of the pulp-enriched cookies. Evaluation of the bioaccessibility of polyphenols from cookies showed that a fraction of polyphenol could be absorbed by the small intestine. This fraction ranged between ~21% and ~25%, according to the sample.


Assuntos
Antioxidantes/química , Fibras na Dieta/análise , Análise de Alimentos , Frutas/química , Polifenóis/metabolismo , Digestão , Prunus persica/química
5.
J Endocrinol Invest ; 43(4): 461-468, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31637675

RESUMO

OBJECTIVE: To evaluate the association between high uric acid (UA), reduced estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) in outpatient children and adolescents with overweight (OW) or obesity (OB). METHODS: Anthropometric, biochemical, hepatic ultrasound and eGFR data were available from 2565 young people with OW/OB (age 5-18 years). eGFR was calculated using the Schwartz's bedside formula and reduced eGFR (ReGFR+) was defined by a value < 90 mL/min/1.73 m2. High UA was defined as ≥ 75th percentile by sex in children and adolescents. RESULTS: The population was stratified in four categories: (1) normal eGFR and absence of NAFLD (ReGFR-/NAFLD-) (n = 1,236); (2) ReGFR+ and absence of NAFLD (ReGFR+/NAFLD- (n = 155); (3) normal eGFR and presence of NAFLD (ReGFR-/NAFLD+) (n = 1019); (4) presence of both conditions (ReGFR+/NAFLD+) (n = 155). Proportions of youth with high UA across the four categories were 17%, 30%, 33% and 46%, respectively (P < 0.0001). Young people with high levels of UA had odds ratio (95% CI) of 2.11 (1.43-3.11) for ReGFR+; 2.82 (2.26-3.45) for NAFLD+; and 5.04 (3.45-7.39) for both conditions (P < 0.0001 for all), independently of major confounders. CONCLUSIONS: High levels of UA were independently associated with ReGFR, NAFLD and the combination of both conditions in young people with OW/OB. The strength of this association was the highest in cases presenting both reduced eGFR and NAFLD. UA may serve as marker to identify patients at risk for these conditions.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Insuficiência Renal Crônica/etiologia , Ácido Úrico/sangue , Criança , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Ultrassonografia
6.
J Endocrinol Invest ; 42(11): 1257-1272, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31073969

RESUMO

Adipose tissue (AT) is one of the largest endocrine organs contributing to metabolic homeostasis. The functional pleiotropism of AT depends on its ability to secrete a large number of hormones, cytokines, extracellular matrix proteins and growth factors, all influencing many local and systemic physiological and pathophysiological processes. In condition of chronic positive energy balance, adipocyte expansion, hypoxia, apoptosis and stress all lead to AT inflammation and dysfunction, and it has been demonstrated that this sick fat is a main risk factor for many metabolic disorders, such as type 2 diabetes mellitus, fatty liver, cardiovascular disease and cancer. AT dysfunction is tightly associated with aberrant secretion of bioactive peptides, the adipocytokines, and their blood concentrations often reflect the expression in the AT. Despite the existence of an association between AT dysfunction and systemic pro-inflammatory state, most of the circulating molecules detectable in obese and dysmetabolic individuals do not identify specifically the condition of sick fat. Based on this premise, this review provides a concise overview of "classic" and novel promising adipocytokines associated with AT inflammation and discusses possible critical approaches to their interpretation in clinical practice.


Assuntos
Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Biomarcadores/metabolismo , Inflamação/imunologia , Inflamação/patologia , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/patologia , Tecido Adiposo/metabolismo , Animais , Humanos , Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismo
7.
Clin Transl Oncol ; 21(12): 1583-1623, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30949930

RESUMO

Progresses in multimodal treatments have significantly improved the outcomes for childhood cancer. Nonetheless, for about one-third of patients with Ewing sarcoma, rhabdomyosarcoma, or osteosarcoma steady remission has remained intangible. Thus, new biomarkers to improve early diagnosis and the development of precision-targeted medicine remain imperative. Over the last decade, remarkable progress has been made in the basic understanding of miRNAs function and in interpreting the contribution of their dysregulation to cancer development and progression. On this basis, this review focuses on what has been learned about the pivotal roles of miRNAs in the regulation of key genes implicated in childhood sarcomas.


Assuntos
Neoplasias Ósseas/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Rabdomiossarcoma/metabolismo , Sarcoma de Ewing/metabolismo , Neoplasias Ósseas/genética , Criança , Regulação para Baixo , Humanos , Osteossarcoma/genética , Rabdomiossarcoma/genética , Sarcoma de Ewing/genética , Regulação para Cima
8.
Osteoporos Int ; 30(4): 907-916, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30715561

RESUMO

Treatment of older adults with hip fracture is a healthcare challenge. Orthogeriatric comanagement that is an integrated model of care with shared responsibility improves time to surgery and reduces the length of hospital stay and mortality compared with orthopedic care with geriatric consultation service and usual orthopedic care, respectively. INTRODUCTION: Treatment of fractures in older adults is a clinical challenge due partly to the presence of comorbidity and polypharmacy. The goal of orthogeriatric models of care is to improve clinical outcomes among older people with hip fractures. We compare clinical outcomes of persons with hip fracture cared according to orthogeriatric comanagement (OGC), orthopedic team with the support of a geriatric consultant service (GCS), and usual orthopedic care (UOC). METHODS: This is a single-center, pre-post intervention observational study with two parallel arms, OGC and GCS, and a retrospective control arm. Hip fracture patients admitted to the trauma ward were assigned by the orthopedic surgeon to the OGC (n = 112) or GCS (n = 108) group. The intervention groups were compared each with others and both with the retrospective control group (n = 210) of older adults with hip fracture. Several clinical indicators are considered, including time to surgery, length of stay, in-hospital, and 1-year mortality. RESULTS: Patients in the OGC (OR 2.62; CI 95% 1.40-4.91) but not those in the GCS (OR 0.74; CI 95% 0.38-1.47) showed a higher probability of undergoing surgery within 48 h compared with those in the UOC. Moreover, the OGC (ß, - 1.08; SE, 0.54, p = 0.045) but not the GCS (ß, - 0.79; SE, 0.53, p = 0.148) was inversely associated with LOS. Ultimately, patients in the OGC (OR 0.31; CI 95 % 0.10-0.96) but not those in the GCS (OR 0.37; CI 95% 0.10-1.38) experienced a significantly lower 1-year mortality rate compared with those in the UOC. All analyses were independent of several confounders. CONCLUSIONS: Older adults with hip fracture taken in care by the OGC showed better clinical indicators, including time to surgery, length of stay and mortality, than those managed by geriatric consultant service or usual orthopedic care.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Serviços de Saúde para Idosos/organização & administração , Fraturas do Quadril/terapia , Fraturas por Osteoporose/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Fixação de Fratura/métodos , Fixação de Fratura/estatística & dados numéricos , Avaliação Geriátrica/métodos , Fraturas do Quadril/complicações , Humanos , Itália , Tempo de Internação/estatística & dados numéricos , Masculino , Modelos Organizacionais , Fraturas por Osteoporose/complicações , Equipe de Assistência ao Paciente/organização & administração , Centros de Traumatologia/organização & administração , Resultado do Tratamento
9.
J Endocrinol Invest ; 42(5): 513-520, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30132286

RESUMO

PURPOSE: Osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC) are matrix glycoproteins which mediate bone mineralization; moreover, their effects on glucose/insulin homeostasis have recently been demonstrated. Higher circulating OPN and OPG levels have been associated with the presence of insulin resistance, atherosclerosis and coronary heart disease. No data are available on contextual changes of these markers in type 2 diabetes mellitus (T2DM). Therefore, aims of this study were to evaluate serum OPN, OPG and OC levels in T2DM patients and their clinical correlates. METHODS: We recruited 83 consecutive T2DM patients referring to our diabetes outpatient clinics at Sapienza, University of Rome, and 71 non-diabetic sex and age-comparable subjects as a control group. Study population underwent metabolic characterization and carotid ultrasound for intima-media thickness measurement. Plasma OPN, OPG and OC were measured by MILLIPLEX Multiplex Assays Luminex. RESULTS: T2DM patients had significantly higher circulating OPN and OPG levels than controls (14.3 ± 13.6 vs 10.6 ± 13.7 ng/ml p < 0.001, 0.70 ± 0.60 vs 0.54 ± 4.1 ng/ml, p = 0.02) while OC levels were similar in the two cohorts (6.35 ± 5.8 vs 7.80 ± 7.0 ng/ml, p = n.s). OPN and OPG positively correlated with greater systolic blood pressure (SBP) values, HOMA-IR and HOMA-ß, and with the presence of dyslipidemia and carotid atherosclerosis. The association between greater OPN and OPG levels and SBP was independent from possible confounders (both p = 0.01). CONCLUSIONS: Circulating OPN and OPG levels are increased in T2DM patients and identify a particularly unfavourable metabolic profile, mostly expressed by higher SBP. Bone peptides may represent novel markers of vascular stress and accelerated atherosclerosis in diabetes, constituting a possible tool for cardiovascular risk stratification in diabetes.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/complicações , Síndrome Metabólica/sangue , Osteopontina/sangue , Osteoprotegerina/sangue , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Seguimentos , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/etiologia , Metaboloma , Pessoa de Meia-Idade , Osteocalcina/sangue , Prognóstico , Fatores de Risco
10.
Neth Heart J ; 26(1): 34-40, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29058206

RESUMO

BACKGROUND: Cardiac magnetic resonance (CMR) has gained a central role in the diagnosis of cardiac amyloidosis (CA). While the diagnostic role of a typical late gadolinium enhancement (LGE) pattern (global subendocardial enhancement coupled with accelerated contrast washout) has been identified, evidence is still conflicting regarding the prognostic role of such examination. METHODS AND RESULTS: We retrospectively analysed all patients referring for CMR at Niguarda Hospital (Milan, Italy) from January 2006 to January 2015 for suspected CA. Primary outcome was all-cause mortality. We identified 42 patients and divided them into 2 groups, according to the presence (Group A) or absence (Group B) of a typical amyloidosis LGE pattern. At the end of the follow-up (median 37 months, interquartile range 10-50 months), 31 patients (74%) had died. The hazard ratio for all-cause death was 3.2 (95% confidence interval [CI] 1.5-6.4, p < 0.01) for Group A versus Group B. Median survival time was 17 months (95% CI 7-42 months) for Group A and 70 months (95% CI 49-94 months) for Group B (p < 0.01). Multivariate analysis did not find any adjunctive predictive role for biventricular volumes and ejection fraction, indexed left ventricular mass, transmitral E/e' at echocardiography, age at diagnosis or serum creatinine. CONCLUSION: In our population, a typical LGE pattern was significantly associated with higher mortality. Moreover, patients with a typical LGE pattern showed a globally worse prognosis. Our data suggest that the LGE pattern may play a central role in prognostic stratification of patients with suspected CA, thus prompting further diagnostic and therapeutic measures.

11.
Acta Diabetol ; 54(10): 961-967, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28836077

RESUMO

AIMS: Interleukin-8 (IL-8) is a chemokine involved in systemic immunity, macrophages infiltration and activation in adipose tissue and may play a significant role in the pathogenesis of type 2 diabetes (T2D) and atherosclerosis. Aims of this study were to evaluate circulating IL-8 levels in adult patients with T2D in comparison with non-diabetic subjects and to describe clinical and biochemical correlates of IL-8 concentration. METHODS: For this cross-sectional study, we enrolled 79 consecutive T2D individuals referring to our diabetes outpatient clinics at Sapienza University of Rome, and 37 sex, age and BMI comparable non-diabetic subjects as a control group. Clinical parameters and medical history were recorded; fasting blood sampling was performed for biochemistry and for measuring serum IL-8, IL-6, TNF-α, CRP, adiponectin and 25(OH)vitamin D [25(OH)D] levels. RESULTS: Patients with T2D exhibited significantly higher serum IL-8 levels than non-diabetic subjects (69.27 ± 112.83 vs. 16.03 ± 24.27 pg/mL, p < 0.001). In diabetic patients, increased IL-8 concentration correlated with higher IL-6 (p < 0.001), TNF-α (p = 0.02), FBG (p = 0.035), HbA1c (p = 0.04) and LDL-C (p = 0.04) and with lower adiponectin (p = 0.02) and 25(OH)D (p = 0.003) concentrations. CONCLUSIONS: Patients with T2D display a marked elevation of circulating IL-8 levels which identify subjects with worse inflammatory, glycometabolic and lipid profile and lower vitamin D levels. Further studies are warranted for evaluating a possible role of IL-8 as a novel marker for risk stratification in T2D patients.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Interleucina-8/sangue , Adiponectina/sangue , Adulto , Biomarcadores/sangue , Calcifediol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue
12.
Nutr Metab Cardiovasc Dis ; 27(9): 830-835, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28755804

RESUMO

BACKGROUND AND AIMS: Hypertension (HTH) is a frequent complication in pediatric obesity. To simplify the screening of HTH in overweight/obese (Ow/Ob) youth, we compared the performance of a new index (High Blood Pressure index, HBPi) with respect to the standard criteria of the IV Report [systolic BP (SBP) and/or diastolic BP (DBP) ≥95th percentile for age, gender and height]. We also compared the performance of HBPi with other simplified indices such as the BP/height ratio and the absolute height-specific BP thresholds. Ten pediatrics' outpatient centers participating in the "CARdiometabolic risk factors in ITALY study" provided medical records of 4225 Ow/Ob children and adolescents (age 6-16 years). METHODS AND RESULTS: Centers were divided into two groups: training set (TS) (n = 2204 participants) and validation set (VS) (n = 2021 participants). The simplified HBPi (mmHg) was: (SBP/2 + DBP/10) - age + (1 × female gender). In the TS, a HBPi value ≥57 mmHg in both children and adolescents had high sensitivity (0.89), specificity (0.97), positive (0.89) and negative (0.97) predictive values in classifying youth at high risk of HTN compared with the IV Report. In the VS, the HBPi showed a better performance than high levels of BP/height ratio and height-specific BP thresholds in classifying individuals at risk of HTN: area under curves 0.95 (0.93-0.96), 0.80 (0.78-0.82), 0.76 (0.74-0.79), respectively; specificities 0.95 (0.94-0.96), 0.69 (0.67-0.72), 0.60 (0.57-0.62), respectively. CONCLUSIONS: HBPi, combining SBP and DBP, gender and age, may help pediatricians to implement HTN screening in Ow/Ob youth.


Assuntos
Determinação da Pressão Arterial , Pressão Sanguínea , Hipertensão/diagnóstico , Programas de Rastreamento/métodos , Obesidade Infantil/diagnóstico , Adolescente , Fatores Etários , Área Sob a Curva , Estatura , Criança , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Itália , Masculino , Obesidade Infantil/epidemiologia , Obesidade Infantil/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Fatores Sexuais
13.
Eur J Vasc Endovasc Surg ; 54(2): 212-219, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28625356

RESUMO

OBJECTIVES: The aim was to investigate whether cardiopulmonary exercise testing (CPET) variables derived from cycle and arm ergonometry correlate, and whether CPET variables and pre-operative N-terminal pro-brain natriuretic peptide (NT-proBNP) have prognostic significance and if the combination of the two has incremental value. METHODS: A prospective observational pilot study was conducted; 70 patients who underwent infra-inguinal bypass surgery were recruited. Pre-operatively subjects underwent CPET with both arm and leg ergonometry, to measure peak oxygen consumption, anaerobic threshold (AT), and ventilatory equivalents. In addition pre-operative serum samples of NT-proBNP were obtained. The primary endpoint was 1 year all-cause mortality; in addition, data were collected on complications, morbidity, length of stay, and major adverse cardiac events (MACE). RESULTS: The 1 year mortality rate was 6%, the overall complications rate was 23%, and the combined incidence of MACE and 1 year mortality was 10%. Cycle ergonometry peak VO2 14 mL/kg/min (RR 5.5, 95% CI 1.4-22.4, p = .007) and AT < 10mL/kg/min (RR 3.0, 95% CI 1.1-7.0, p = .03) were predictors of post-operative complications. Pre-operative NT-proBNP > 320 ng/L (RR 18, 95% CI 2.5-140 p = .0003) was the sole predictor of 1 year mortality or MACE. CONCLUSION: The measurement of pre-operative NT-proBNP in peripheral vascular disease patients undergoing infra-inguinal bypass can predict 1 year mortality and MACE. CPET variables from cycle ergonometry are predictors of post-operative complications in this patient group.


Assuntos
Teste de Esforço , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Doença Arterial Periférica/cirurgia , Enxerto Vascular , Idoso , Limiar Anaeróbio , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Consumo de Oxigênio , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Enxerto Vascular/efeitos adversos , Enxerto Vascular/mortalidade
14.
Nutr Metab Cardiovasc Dis ; 26(5): 407-13, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27052925

RESUMO

BACKGROUND AND AIMS: 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM in a cohort of Italian adults with T2DM and in non-diabetic controls. To add further insight into the role of VDR gene we explored whether this association begins early in life in overweight/obese children, or becomes manifest only in adulthood. METHODS AND RESULTS: As many as 1788 adults and 878 children were genotyped for the rs11568820 polymorphism. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin-resistance and secretion were also calculated. The AA genotype was significantly more frequent in adults with T2DM compared to controls (7.5% vs. 4.6%, P = 0.037), and conferred a higher risk of T2DM (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of ß-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk. CONCLUSIONS: Our study demonstrates for the first time that VDR gene AA carriers have higher risk of T2DM and impaired insulin secretion. In children, the association between AA homozygous and high-normal 2h glucose suggests that mild alterations associated with this genotype may appear early in life.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Insulina/sangue , Síndrome Metabólica/genética , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Adolescente , Adulto , Idade de Início , Biomarcadores/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Teste de Tolerância a Glucose , Heterozigoto , Homozigoto , Humanos , Insulina/metabolismo , Resistência à Insulina/genética , Secreção de Insulina , Itália , Modelos Lineares , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Razão de Chances , Obesidade Infantil/sangue , Obesidade Infantil/diagnóstico , Fenótipo , Receptores de Calcitriol/metabolismo , Fatores de Risco
15.
J Thromb Haemost ; 13(8): 1468-74, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26083275

RESUMO

BACKGROUND: The homologous coagulation factor X (FX), VII (FVII), IX (FIX) and protein C (PC) display striking differences in the carboxyl-terminus, with that of FX being the most extended. This region is essential for FVII, FIX and PC secretion. OBJECTIVES: To provide experimental evidence for the role of the FX carboxyl-terminus. METHODS: Recombinant FX (rFX) variants were expressed in multiple eukaryotic cell systems. Protein and activity levels were evaluated by ELISA, coagulant and amidolytic assays. RESULTS AND DISCUSSION: Expression of a panel of progressively truncated rFX variants in HEK293 cells revealed that the deletion of up to 21 residues in the carboxyl-terminus did not significantly affect secreted protein levels, as confirmed in HepG2 and BHK21 cells. In contrast, chimeric rFX-FVII variants with swapped terminal residues showed severely reduced levels. The truncated rFX variants revealed normal amidolytic activity, suggesting an intact active site. Intriguingly, these variants, which included that resembling the activated FXß form once cleaved, also displayed remarkable or normal pro-coagulant capacity in PT- and aPTT-based assays. This supports the hypothesis that subjects with nonsense mutations in the FX carboxyl-terminus, so far never identified, would be asymptomatic. CONCLUSIONS: For the first time we demonstrate that the FX carboxyl-terminal region downstream of residue K467 is not essential for secretion and provides a modest contribution to pro-coagulant properties. These findings, which might suggest an involvement of the carboxyl-terminal region in the divergence of the homologous FX, FVII, FIX and PC, help to interpret the mutational pattern of FX deficiency.


Assuntos
Coagulação Sanguínea , Fator X/metabolismo , Hepatócitos/metabolismo , Animais , Cricetinae , Fator X/química , Fator X/genética , Células HEK293 , Células Hep G2 , Humanos , Mutagênese Sítio-Dirigida , Mutação , Tempo de Tromboplastina Parcial , Estrutura Terciária de Proteína , Tempo de Protrombina , Relação Estrutura-Atividade , Transfecção
16.
Biochim Biophys Acta ; 1854(10 Pt A): 1351-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26012870

RESUMO

Alterations in coagulation factor X (FX) activation, mediated by the extrinsic VIIa/tissue factor (FVIIa/TF) or the intrinsic factor IXa/factor VIIIa (FIXa/FVIIIa) complexes, can result in hemorrhagic/prothrombotic tendencies. However, the molecular determinants involved in substrate recognition by these enzymes are poorly defined. Here, we investigated the role of arginine 386 (chymotrypsin numbering c202), a surface-exposed residue on the FX catalytic domain. The naturally occurring FX386Cys mutant and FX386Ala variant were characterized. Despite the unpaired cysteine, recombinant (r)FX386Cys was efficiently secreted (88.6±21.3% of rFXwt) and possessed normal clearance in mice. rFX386Cys was also normally activated by FVIIa/TF and displayed intact amidolytic activity. In contrast, rFX386Cys activation by the FIXa/FVIIIa complex was 4.5-fold reduced, which was driven by a decrease in the kcat (1.6∗10(-4) s(-1) vs 5.8∗10(-4) s(-1), rFXwt). The virtually unaltered Km (70.6 nM vs 55.6nM, rFXwt) suggested no major alterations in the FX substrate exosite. Functional assays in plasma supplemented with rFX386Cys indicated a remarkable reduction in the thrombin generation rate and thus in coagulation efficiency. Consistently, the rFX386Ala variant displayed similar biochemical features suggesting that global changes at position 386 impact the intrinsic pathway activation. These data indicate that the FXArg386 is involved in FIXa/FVIIIa-mediated FX activation and help in elucidating the bleeding tendency associated with the FX386Cys in a rare FX deficiency case. Taking advantage of the unpaired cysteine, the rFX386Cys mutant may be efficiently targeted by thiol-specific ligands and represent a valuable tool to study FX structure-function relationships both in vitro and in vivo.


Assuntos
Coagulação Sanguínea/genética , Fator X/metabolismo , Fator Xa/metabolismo , Mutação , Animais , Testes de Coagulação Sanguínea , Domínio Catalítico , Fator IXa/genética , Fator IXa/metabolismo , Fator VIIIa/genética , Fator VIIIa/metabolismo , Fator X/química , Fator X/genética , Fator Xa/química , Fator Xa/genética , Células HEK293 , Humanos , Cinética , Metaloendopeptidases/genética , Metaloendopeptidases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Ligação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Trombina/genética , Trombina/metabolismo
17.
Arq. bras. med. vet. zootec ; 65(1): 289-293, fev. 2013. tab
Artigo em Português | LILACS | ID: lil-667568

RESUMO

O presente experimento foi conduzido com o objetivo de avaliar a porcentagem de inclusão da espécie forrageira Gliricidia sepium (Jacq.) Walq na confecção do sal forrageiro de gliricídia, por meio de características de carcaça e de não componentes da carcaça de cordeiros. Foram utilizados 30 cordeiros mestiços da raça Santa Inês, não castrados, com aproximadamente 180 dias de idade, peso vivo médio de 25kg, confinados, num delineamento experimental inteiramente ao acaso, com cinco tratamentos e seis repetições, em que os tratamentos foram constituídos de zero (100% de NaCl), 93, 95, 97 e 99% de inclusão de feno de gliricídia (7, 5, 3 e 1% de NaCl na formulação do sal forrageiro, respectivamente). A suplementação com sal forrageiro de gliricídia não afetou (P>0,05) o peso vivo ao abate em jejum (28,39kg), peso de carcaça quente (9,76kg), rendimento de carcaça quente (34,12%), o peso de carcaça fria (9,42kg), o rendimento de carcaça fria (32,95%), as perdas de peso por resfriamento (3,40%), assim como o peso de vísceras brancas (2,19kg) e o peso de vísceras vermelhas (1,29kg). Porcentagem de inclusão de até 99% de gliricídia na confecção de sal forrageiro não altera (P>0,05) as características de carcaça e de não componentes da carcaça de cordeiros.


The experiment was conducted to evaluate the inclusion of Gliricidia sepium (Jacq.) Walq forage species for the confection of the fodder salt gliricidia according to the characteristics of carcass and non-carcass components of lambs. Thirty confined, not castrated crossbred Santa Inês lambs, ageing approximately 180 days, with mean live body weight of 25kg, were distributed in a completely randomized design, with five treatments and six repetitions. Treatments were zero (100% NaCl), 93, 95, 97 and 99% inclusion of gliricidia hay (7, 5, 3 and 1% NaCl in the formulation of fodder salt, respectively). The supplementation with gliricidia fodder salt did not affect (P>0.05) the fasting live body weight (28.39kg), hot carcass weight (9.76kg), hot carcass yield (34.12%), cold carcass weight (9.42kg), cold carcass yield (32.95%), chilling loss (3.40%), or white (2.19kg) and red viscera weight (1.29kg). The inclusion of up to 99% gliricidia in the production of fodder salt did not affect (P>0.05) the characteristics of carcass and non-carcass components of lambs.


Assuntos
Animais , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Ovinos/anatomia & histologia , Ovinos/anormalidades , Matadouros
18.
J Endocrinol Invest ; 35(2): 154-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21532330

RESUMO

BACKGROUND: Diabetes mellitus is frequently observed in patients with acromegaly. Current therapies for acromegaly may impact glucose regulation, influencing insulin sensitivity and secretion. The question whether these therapies modify control and progression of diabetes once present is still open. AIM: Aim of our study is to analyze glucose control in acromegalic patients with diabetes, evaluating the relation with treatments for GH excess and for diabetes. METHODS: Seventy patients with acromegaly and diabetes were studied. Duration and treatments of acromegaly and diabetes were recorded, together with clinical and metabolic parameters. RESULTS: Most patients (92.8%) were treated with somatostatin analogs (SSA), either alone or in combination with dopamine-agonists (20%) or pegvisomant (15.7%); 7.1% of patients had been treated by surgery alone. Metformin (65.7%), alone or in combination with other hypoglycemic drugs, was the most frequent treatment for diabetes, followed by insulin (21.5%). Only 15.7% were treated with diet alone. The whole cohort showed a very good control of diabetes and acromegaly. Median glycated hemoglobin was 6.4% (5.9-7). IGF-I was within normal range for age in most patients. No relation was observed between duration of acromegaly or diabetes and metabolic control. SSA had a negative effect on insulin secretion, but these effects did not influence glucose control. Finally, we observed a low prevalence of nephropathy (6%) and retinopathy (20%). CONCLUSIONS: Our study shows that a good control of hyperglycemia can be obtained with success in the majority of acromegalic patients with diabetes, independently of the type of treatment for GH excess.


Assuntos
Acromegalia/metabolismo , Acromegalia/terapia , Glicemia/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Acromegalia/sangue , Acromegalia/complicações , Idoso , Glicemia/efeitos dos fármacos , Estudos de Coortes , Complicações do Diabetes/sangue , Complicações do Diabetes/terapia , Diabetes Mellitus/sangue , Agonistas de Dopamina/uso terapêutico , Procedimentos Cirúrgicos Endócrinos , Hemoglobinas Glicadas/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/terapia , Pessoa de Meia-Idade , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico
19.
Diabet Med ; 28(8): 896-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21749442

RESUMO

AIMS: Type 1 diabetes and autoimmune thyroiditis are common autoimmune diseases characterized by the presence of autoantibodies against tissue-specific components. Non-thyroid-specific autoantibodies are frequent in patients with autoimmune thyroiditis. The prevalence of Type 1 diabetes autoantibodies in patients with autoimmune thyroiditis is unknown. METHODS: The prevalence of Type 1 diabetes autoantibodies (GAD and IA2) was analysed in 236 Sardinian children and adolescents with autoimmune thyroiditis. GAD and IA2 antibodies were measured at the time of the diagnosis of autoimmune thyroiditis and re-evaluated after 1 year in the children who were shown to be positive. Autoantibody prevalence was evaluated in 949 healthy age-matched controls. RESULTS: The prevalence of GAD and/or IA2 antibodies was 8% in the children and adolescents with autoimmune thyroiditis and 4.1% in control subjects (P = 0.017). When Type 1 diabetes autoantibodies were separately analysed, the difference remained significant for IA2 (3.39% in autoimmune thyroiditis vs. 1.16% in control subjects, P = 0.012), but not for GAD (5.1% in autoimmune thyroiditis vs. 3.79% in control subjects, P = 0.367). Seven of 10 children with autoimmune thyroiditis and detectable Type 1 diabetes autoantibodies at the diagnosis remained positive after 1 year. In the course of 2 years of follow-up, two patients who were positive for Type 1 diabetes autoantibodies at the time of diagnosis of autoimmune thyroiditis developed diabetes. CONCLUSIONS: This is the first study reporting the prevalence of Type 1 diabetes autoantibodies in a selected cohort of genetically homogeneous children and adolescents with autoimmune thyroiditis. The main finding was that the prevalence of Type 1 diabetes autoantibodies and of newly diagnosed Type 1 diabetes in patients with autoimmune thyroiditis was significantly higher than that observed in the general paediatric population, suggesting that children with autoimmune thyroiditis are at increased risk of developing Type 1 diabetes.


Assuntos
Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Glutamato Descarboxilase/imunologia , Proteínas Tirosina Fosfatases/imunologia , Tireoidite Autoimune/imunologia , Adolescente , Autoanticorpos/classificação , Criança , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Glutamato Descarboxilase/classificação , Humanos , Itália/epidemiologia , Masculino , Proteínas Tirosina Fosfatases/classificação
20.
Transplant Proc ; 42(6): 2254-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20692458

RESUMO

Human resources represent at the moment the most critical factor in an hospital setting characterized by a high rate of staff turnover. It is important to ensure a consistent level of expertise and knowledge of professionals who work in health care facilities to provide quality services and simultaneously support the implementation of strategies for patient safety. Unfortunately, the development of effective interventions for training newly added staff and self-evaluation of skills possessed by trained staff are closely related to understanding critical aspects of the organization. At the new Center for Bone Marrow Transplantation and Blood Transfusion Service in Meyer Hospital, during the last year, a group of professional nurses and technicians completed a specific plan to train new staff and, at the same time, a program of self-assessment of skills for experienced staff. The main purpose of this project was to promote skills development by newly added as well as experienced staff, to identify areas of weaknesses, and to correct them with training (organized by the hospital, departmental, or individual) designed to improve performance.


Assuntos
Acreditação/normas , Transplante de Medula Óssea/normas , Pacientes , Recursos Humanos em Hospital/normas , Autoavaliação (Psicologia) , Doadores de Tecidos , Autoavaliação Diagnóstica , Unidades Hospitalares/normas , Humanos , Pessoal de Laboratório Médico/normas , Recursos Humanos de Enfermagem Hospitalar/normas , Segurança
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