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1.
Int J Mol Sci ; 21(2)2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31940853

RESUMO

Immune cell subsets and microRNAs have been independently proposed as type 1 diabetes (T1D) diagnostic and/or prognostic biomarkers. Here, we aimed to analyze the relationships between peripheral blood circulating immune cell subsets, plasmatic microRNAs, and T1D. Blood samples were obtained from both children with T1D at diagnosis and age-sex matched healthy controls. Then, immunophenotype assessed by flow cytometry was coupled with the quantification of 60 plasmatic microRNAs by quantitative RT-PCR. The associations between immune cell frequency, plasmatic microRNAs, and the parameters of pancreatic loss, glycemic control, and diabetic ketoacidosis were assessed by logistic regression models and correlation analyses. We found that the increase in specific plasmatic microRNAs was associated with T1D disease onset (let-7c-5p, let-7d-5p, let-7f-5p, let-7i-5p, miR-146a-5p, miR-423-3p, and miR-423-5p), serum C-peptide concentration (miR-142-5p and miR-29c-3p), glycated hemoglobin (miR-26a-5p and miR-223-3p) and the presence of ketoacidosis (miR-29c-3p) more strongly than the evaluated immune cell subset frequency. Some of these plasmatic microRNAs were shown to positively correlate with numbers of blood circulating B lymphocytes (miR-142-5p) and CD4+CD45RO+ (miR-146a-5p and miR-223-3p) and CD4+CD25+ cells (miR-423-3p and miR-223-3p) in children with T1D but not in healthy controls, suggesting a disease-specific microRNA association with immune dysregulation in T1D. In conclusion, our results suggest that, while blood co-circulating extracellular microRNAs and immune cell subsets may be biologically linked, microRNAs may better provide powerful information about T1D onset and severity.

2.
Growth Horm IGF Res ; 48-49: 9-15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487604

RESUMO

Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhGH). These patients are highly sensitive to rhGH and the standard doses suggested by the international guidelines often result in IGF-1 above the normal range. We aimed to evaluate 1 the proper rhGH dose to optimize auxological outcomes and to avoid potential overtreatment, and 2 which patients are more sensitive to rhGH. In this multicenter real-life study, we recruited 215 patients with PWS older than 1 year, on rhGH at least for 6 months, from Italian Centers for PWS care. We collected auxological parameters, rhGH dose, IGF-1 at recruitment and (when available) at start of treatment. The rhGH dose was 4.3 (0.7/8.4) mg/m2/week. At recruitment, IGF-1 was normal in 72.1% and elevated in 27.9% of the patients. In the group of 115 patients with IGF-1 available at start of rhGH, normal pretreatment IGF-1 and uniparental disomy were associated with elevated IGF-1 during the therapy. No difference in height and growth velocity was found between patients treated with the highest and the lowest range dose. The rhGH dose prescribed in Italy seems lower than the recommended one. Normal pretreatment IGF-1 and uniparental disomy are risk factors for elevated IGF-1. The latter seems to be associated with higher sensitivity to GH. In case of these risk factors, we recommend a more accurate titration of the dose to avoid overtreatment and its potential side effects.

3.
Acta Diabetol ; 56(12): 1315-1321, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31493030

RESUMO

AIM: To assess the association between alcohol consumption and/or cigarette smoking with other unhealthy behaviors and clinical cardiovascular risk factors in youth with type 1 diabetes. METHODS: Two hundred and twenty-eight youth with type 1 diabetes (age 13-19 years) were consecutively enrolled in three Regional Pediatric Diabetes Centers in Italy. Demographic, anthropometric, lifestyle (adherence to the Mediterranean diet pattern and sports participation) and laboratory parameters were compared among youth reporting isolated or combined alcohol consumption and/or cigarette smoking. RESULTS: Ten percent of the youth reported alcohol consumption, 10% cigarette smoking and 6% both alcohol and cigarette use; 74% did not report alcohol or cigarette use. Compared to non-drinker non-smoker youth, smokers showed significantly higher percentages of each of the behavioral and clinical cardiovascular risk factors. Drinkers showed a significantly higher proportion of abdominal adiposity, dyslipidemia and poor adherence to the Mediterranean diet. Alcohol consumption was independently associated with both dyslipidemia and high glycosylated hemoglobin. CONCLUSIONS: Our findings emphasize the need to increase the awareness of youth with T1D about the negative impact of alcohol drinking on cardiovascular risk, since the effects of alcohol might be underestimated with respect to the well-known detrimental effects of smoking. Clustering of unhealthy lifestyle should be discouraged in type 1 diabetes youth in order to promote cardiovascular protection.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Fumar Cigarros/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Angiopatias Diabéticas/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Doenças Cardiovasculares/etiologia , Fumar Cigarros/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Itália/epidemiologia , Estilo de Vida , Masculino , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Adulto Jovem
4.
Cells ; 8(7)2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31331105

RESUMO

HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity.


Assuntos
Doença Celíaca/genética , Diabetes Mellitus Tipo 1/genética , Regulação da Expressão Gênica , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Adolescente , Alelos , Apresentação do Antígeno/genética , Autoimunidade/genética , Doença Celíaca/imunologia , Criança , Diabetes Mellitus Tipo 1/imunologia , Predisposição Genética para Doença , Humanos
5.
Diabetes Res Clin Pract ; 155: 107781, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279959

RESUMO

AIMS: To analyze the factors associated with non-albuminuric reduced estimated glomerular filtration rate (NAeGFR-) phenotype in young people with type 1 diabetes (T1DM). METHODS: In this cross-sectional study were enrolled 140 outpatient diabetic children (age 7-18 years), consecutively observed in the period 2016-2017. Eighteen subjects with microalbuminuria (defined as albumin excretion rate ≥ 30 mg/24 h) were excluded. Fasting HbA1c, uric acid (UA), neutrophils and lymphocytes count were recorded. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz's bed-side formula and reduced eGFR was defined by a value <90 mL/min/1.73 m2. RESULTS: Out of 122 subjects analyzed, 76 (62%) showed normal eGFR and 46 (38%) showed NAeGFR- phenotype. They were characterized by higher prevalence of male sex (57% vs 33%, p = 0.010), autoimmune diseases (26% vs 12%, p = 0.043), high UA levels (4.0 ±â€¯0.9 vs 3.3 ±â€¯0.9 mg/dl, p < 0.0001) and high Neutrophils/Lymphocytes ratio (1.5 [1.2-2.0] vs 1.3 [1.0-1.8], p = 0.023). CONCLUSIONS: In our population, the prevalence on NAeGFR- phenotype is 38% and it is associated with male sex, high levels of UA, presence of other autoimmune diseases and low-grade inflammation. It should encourage pediatricians to monitor early both eGFR and UA in order to intercept diabetic youth more likely prone to develop progressive renal impairment.


Assuntos
Albuminas/análise , Diabetes Mellitus Tipo 1/fisiopatologia , Taxa de Filtração Glomerular , Insuficiência Renal/epidemiologia , Adolescente , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Hemoglobina A Glicada/análise , Humanos , Incidência , Itália/epidemiologia , Masculino , Fenótipo , Prevalência , Ácido Úrico/análise
6.
Health Promot Int ; 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31011751

RESUMO

Though classroom time has been identified as a contributing factor to sedentary behavior, school has been recognized as the main educational setting providing physical activity (PA) opportunities. The purpose of this study was to develop and evaluate the feasibility of a classroom-based intervention which integrates PA during the school time, and assess its potential effect on reducing inactivity in primary school children. The intervention was performed in a sample of 47 children attending a primary school in the south of Italy and it was structured in two sessions of classroom active breaks (CABs) in three school days a week, shared with and supervised by the teachers. CABs showed an overall potential positive effect on the reduction of inactivity of ∼12 min and an equivalent increase in PA levels, of which 5 min were of moderate/vigorous intensity. Girls showed lower time spent in light and moderate PA and higher amount of inactivity than boys and responded better to the intervention. The satisfaction of children and teachers was high. CABs program is a safe tool to reduce inactivity and increase moderate/vigorous PA. Designing structured exercise breaks adapted in a flexible way to meet the needs of the school curriculum program may increase the feasibility of such PA program in the schools.

7.
Curr Diab Rep ; 18(12): 140, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30370431

RESUMO

PURPOSE OF REVIEW: Non-diabetic hyperglycemia (NDHY) is a pathological condition that is not yet well known. The aim of this review is to examine approaches for management of this condition. RECENT FINDINGS: While it is well known that persistent hyperglycemia in diabetes affects immune response and risk for diabetes-related micro- and macrovascular complications, little is known about the biological effects of transient NDHY, particularly in the pediatric age group. Stress HY (SHY) is typically defined as blood glucose > 8.33 mmol/L (150 mg/dL) during physical stress, resolving spontaneously after dissipation of acute illness in patients without known diabetes. Based on the literature and clinical practice, two situations can be classified: (1) SHY1, which occurs during severe and prolonged illness and under serious life-threatening conditions, mainly in emergency situations and in resuscitation areas; and (2) SHY2, which occurs during acute illness, mainly in non-life-threatening conditions. Furthermore, (NDHY) among pediatric patients can be induced by drugs; the most frequent conditions are secondary to (1) steroid therapy and (2) antineoplastic/immunosuppressive therapy.


Assuntos
Diabetes Mellitus/patologia , Hiperglicemia/terapia , Glicemia/metabolismo , Criança , Estado Terminal , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/fisiopatologia , Estresse Fisiológico
8.
Ital J Pediatr ; 44(1): 88, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30064525

RESUMO

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.


Assuntos
Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/terapia , Adolescente , Criança , Pré-Escolar , Consenso , Endocrinologia , Humanos , Lactente , Recém-Nascido , Itália , Pediatria , Sociedades Médicas
9.
Orphanet J Rare Dis ; 13(1): 115, 2018 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-30005674

RESUMO

BACKGROUND: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by recurrent edema of unpredictable frequency and severity. Stress, anxiety, and low mood are among the triggering factors most frequently reported. Impaired regulation and processing of emotions, also known as alexithymia, may influence outcomes. The aim of this study was to confirm the presence of alexithymia and stress in children with C1-INH-HAE, to determine whether they are also present in children affected by other chronic diseases, and to investigate their relationship with C1-INH-HAE severity. Data from children with C1-INH-HAE (n = 28) from four reference centers in Italy were compared with data from children with type 1 diabetes (T1D; n = 23) and rheumatoid arthritis (RA; n = 25). Alexithymia was assessed using the Alexithymia Questionnaire for Children scale; perceived stress was assessed using the Coddington Life Event Scale for Children (CLES-C). RESULTS: Mean age (standard deviation [SD]) in the C1-INH-HAE, T1D, and RA groups was 11.8 (3.3), 11.7 (2.9), and 11.1 (2.6) years, respectively. Mean C1-INH-HAE severity score was 5.9 (2.1), indicating moderate disease. Alexithymia scores were similar among disease groups and suggestive of difficulties in identifying and describing emotions; CLES-C scores tended to be worse in C1-INH-HAE children. C1-INH-HAE severity was found to correlate significantly and positively with alexithymia (p = 0.046), but not with perceived stress. Alexithymia correlated positively with perceived stress. CONCLUSIONS: Alexithymia is common in children with chronic diseases. In C1-INH-HAE, it may result in increased perceived stress and act as a trigger of edema attacks. Comprehensive management of C1-INH-HAE children should consider psychological factors.


Assuntos
Angioedemas Hereditários/metabolismo , Angioedemas Hereditários/psicologia , Proteína Inibidora do Complemento C1/metabolismo , Adolescente , Ansiedade/metabolismo , Criança , Progressão da Doença , Emoções/fisiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários
11.
Eur J Pediatr ; 177(9): 1367-1370, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29318372

RESUMO

Sleep-related disordered breathing (SDB) is very common in paediatric patients affected by Prader-Willi Syndrome (PWS). However, data addressing SBD patterns and their management are lacking. The aim of the present study was to analyse SDB features in 14 PWS patients (age range, 8 months-17 years). Polygraphic registration (PG) during a 12-h nocturnal sleep was performed in all patients. Obstructive and central apnoea indices and oxygen saturation (SpO2) were recorded along with demographic and clinical data. Obstructive sleep apnoea (OSA) was diagnosed in 13/14 patients (92.9%); the mean obstructive apnoea-hypopnea index (OAHI) was 7.6 ± 4.2 events/h with a mean central apnoea index (CAI) of 0.7 ± 1.04 events/h. Time spent with SpO2 < 90% was of 0.02% [range 0-23%], with a mean oxygen desaturation index of 12.1 ± 6.9 events/h. No correlation was found between OAHI and body mass index (mean BMI 28 ± 9.8 kg/m2 and BMI z-score 2.7 ± 1.7). CONCLUSION: OSA was the predominant sleep-related disorder in our PWS patients, not associated with age or obesity, and appeared more severe than previously reported. Further studies addressing the underlying mechanisms are necessary in larger study populations to better design the most appropriate clinical approach. What is Known: • Sleep-related patterns and their management are very limited in patients with Prader-Willi syndrome. What is New: • Severe obstructive sleep apnoea is the most frequent sleep-related disorder in our case series.


Assuntos
Síndrome de Prader-Willi/complicações , Apneia Obstrutiva do Sono/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Polissonografia , Sono , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico
12.
J Pediatr ; 194: 94-99, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29229450

RESUMO

OBJECTIVES: To provide further evidence regarding the relationship between obesity and gastroesophageal reflux disease (GERD) in children, through the use of 13C-octanoic acid breath test for gastric emptying time (GET) assessment and esophageal multichannel intraluminal impedance pH-testing (MII-pH). STUDY DESIGN: Obese children aged 4-17 years completed a questionnaire investigating reflux symptoms, the presence of functional gastrointestinal disorders, and quality of life. A subgroup of obese patients with and without GERD symptoms were asked to undergo 13C-octanoic acid breath test. Symptomatic patients were also required to undergo MII-pH. Age- and sex- matched asymptomatic nonobese children were enrolled as a comparison group. RESULTS: Of 113 enrolled patients, 44 (38.9%) reported reflux symptoms; 22 of the 44 underwent MII-pH. Their mean reflux index was 14.6%, and their mean number of daily reflux episodes was 51.8. The mean T½ GET of symptomatic was 107.6 minutes vs 116.5 minutes in asymptomatic obese children. Healthy nonobese children had a mean T½ GET of 100.1 minutes. The mean GET of symptomatic obese patients having >70 daily reflux events was 121.8 vs 87.6 minutes of patients with <70 daily reflux events (P <.05). Both symptomatic and asymptomatic obese patients had a worse quality of life than nonobese (P = 0.003 and P = 0.0002, respectively); a narrow waist circumference was directly related to GET (P = 0.01). CONCLUSIONS: A high percentage of obese children and adolescents experience GERD symptoms. GET was directly related to the narrow waist circumference of obese children with GERD and was significantly delayed in obese children with increased reflux events. Both symptomatic and asymptomatic obese patients had a worse quality of life compared with nonobese healthy patients.


Assuntos
Esvaziamento Gástrico/fisiologia , Gastroenteropatias/epidemiologia , Obesidade Pediátrica/complicações , Obesidade Pediátrica/fisiopatologia , Qualidade de Vida , Adolescente , Estudos de Casos e Controles , Criança , Monitoramento do pH Esofágico , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Humanos , Masculino , Avaliação de Sintomas
13.
Acta Diabetol ; 54(12): 1073-1080, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28914364

RESUMO

AIMS: Management of type 1 diabetes mellitus (T1DM) influences several aspects of life, such as adherence to healthy lifestyle habits and health-related quality of life (HRQoL). Our aim was to evaluate the association between unhealthy lifestyle habits and HRQoL in adolescents and young adults with T1DM. METHODS: Two hundred and forty-two Caucasian patients (13-19 years) consecutively enrolled over a 12-month period in three Regional Pediatric Diabetes Centers in Italy. Demographics, clinical, and laboratory parameters, adherence to lifestyle habits (Mediterranean Diet assessed by KIDMED, Physical Activity levels and sedentary behavior by questionnaire) considered either separately or in cluster, and HRQoL by Pediatric Quality of Life Inventory Diabetes Module (PedsQL 3.0 DM) were collected. Metabolic control was determined by HbA1cmean of previous year. RESULTS: Only 15 (6.2%) patients fulfilled the cluster of three healthy lifestyle habits without gender differences (p = 0.353); 62 (25.6%) had 1 unhealthy lifestyle habit, and 165 (68.2%) had ≥2. Adolescents meeting physical activity recommendations had better PedsQL scores than those who did not meet. PedsQL total score and specific sub-scales decreased in patients with unhealthy lifestyle habits. High PedsQL was significantly associated with being male, living in South Italy, having lower HbA1c mean levels, and reporting lower adherence to unhealthy lifestyle habits. CONCLUSIONS: The clustering of unhealthy lifestyle habits is associated with reduced HRQoL in adolescents and young adults with T1DM. Promoting multiple behavior changes may be a useful approach to improve the health status and the HRQoL in youths with T1DM.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Hábitos , Nível de Saúde , Estilo de Vida , Qualidade de Vida , Adolescente , Adulto , Criança , Diabetes Mellitus Tipo 1/psicologia , Dieta Mediterrânea , Exercício , Feminino , Humanos , Itália/epidemiologia , Masculino , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
14.
Diabetes Ther ; 8(5): 1187-1190, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28770464

RESUMO

Diabetes mellitus is the most common comorbidity in cystic fibrosis (CF). Recently, more attention has been paid to early glucose metabolism derangements (GMDs). The subject of this report is a female patient, affected by CF since 3 months of age. She presented with intermittent diabetes during early childhood. At the age of 10 years, oral glucose tolerance test (OGTT) was performed and showed glucose intolerance (IGT) status; glargine insulin therapy was started. At the age of 13 years, CF-related diabetes with fasting hyperglycemia occurred, so rapid insulin at meals was added. During the following year, clinical and nutritional status improved. Stable clinical conditions were observed in the following 3 years. This is the first case of very long-term follow-up concerning a CF patient with GMDs. Our case confirms the importance of paying attention to early GMDs in very young CF patients and seems to suggest that earlier therapy could ameliorate CF natural history.

16.
Am J Med Genet A ; 170(8): 2196-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27256967

RESUMO

In childhood, several rare genetic diseases have overlapping symptoms and signs, including those regarding growth alterations, thus the differential diagnosis is sometimes difficult. The proband, aged 3 years, was suspected to have Silver-Russel syndrome because of intrauterine growth retardation, postnatal growth retardation, typical facial dysmorphic features, macrocephaly, body asymmetry, and bilateral fifth finger clinodactyly. Other features were left atrial and ventricular enlargement and patent foramen ovale. Total X-ray skeleton showed hypoplasia of the twelfth rib bilaterally and of the coccyx, slender long bones with thick cortex, and narrow medullary channels. The genetic investigation did not confirm Silver-Russel syndrome. At the age of 5 the patient developed an additional sign: hepatomegaly. Array CGH revealed a 147 kb deletion (involving TRIM 37 and SKA2 genes) on one allele of chromosome 17, inherited from his mother. These results suggested Mulibrey nanism. The clinical features were found to fit this hypothesis. Sequencing of the TRIM 37 gene showed a single base change at a splicing locus, inherited from his father that provoked a truncated protein. The combined use of Array CGH and DNA sequencing confirmed diagnosis of Mulibrey nanism. The large deletion involving the SKA2 gene, along with the increased frequency of malignant tumours in mulibrey patients, suggests closed monitoring for cancer of our patient and his mother. Array CGH should be performed as first tier test in all infants with multiple anomalies. The clinician should reconsider the clinical features when the genetics suggests this. © 2016 Wiley Periodicals, Inc.


Assuntos
Nanismo de Mulibrey/diagnóstico , Nanismo de Mulibrey/genética , Mutação , Proteínas Nucleares/genética , Pré-Escolar , Hibridização Genômica Comparativa , Análise Mutacional de DNA , Humanos , Masculino , Linhagem , Exame Físico , Sítios de Splice de RNA , Radiografia , Análise de Sequência de DNA
17.
Acta Diabetol ; 53(3): 493-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26687197

RESUMO

AIMS: To identify metabolic phenotypes at increased risk of impaired glucose tolerance (IGT) in Italian overweight/obese children (n = 148, age 5-10 years) and adolescents (n = 531, age 10-17.9 year). METHODS: Phenotypes were defined as follows: obesity by the 95th cut-points of the Center for Disease Control body mass index reference standards, impaired fasting glucose (fasting plasma glucose ≥100 mg/dl), high circulating triglycerides (TG), TG/HDL cholesterol ≥2.2, waist-to-height ratio (WTHR) >0.6, and combination of the latter with high TG or TG/HDL cholesterol ≥2.2. RESULTS: In the 148 obese children, TG/HDL-C ≥ 2.2 (OR 20.19; 95 % CI 2.50-163.28, p = 0.005) and the combination of TG/HDL-C ≥ 2.2 and WTHR > 0.60 (OR 14.97; 95 % CI 2.18-102.76, p = 0.006) were significantly associated with IGT. In the 531 adolescents, TG/HDL-C ≥ 2.2 (OR 1.991; 95 % CI 1.243-3.191, p = 0.004) and the combination with WTHR > 0.60 (OR 2.24; 95 % CI 1.29-3.87, p = 0.004) were associated with significantly increased risk of IGT. In the whole sample, having high TG levels according to the NIH National Heart, Lung and Blood Institute Expert Panel was not associated with an increased risk of presenting IGT. CONCLUSIONS: TG/HDL-C ratio can be useful, particularly in children, to identify obese young patients at risk of IGT. Its accuracy as screening tool in a general population needs to be verified. The combination of TG/HDL-C ratio and WTHR > 0.6 did not improve prediction. Having high TG according to the NIH definition was not associated with increased risk of developing IGT.


Assuntos
Intolerância à Glucose/sangue , Programas de Rastreamento/métodos , Obesidade/sangue , Adolescente , Estudos de Casos e Controles , Criança , HDL-Colesterol/sangue , Feminino , Intolerância à Glucose/epidemiologia , Humanos , Itália , Lipoproteínas HDL/sangue , Masculino , Obesidade/epidemiologia , Triglicerídeos/sangue
18.
Mol Cytogenet ; 8: 96, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26689541

RESUMO

BACKGROUND: The chromothripsis is a biological phenomenon, first observed in tumors and then rapidly described in congenital disorders. The principle of the chromothripsis process is the occurrence of a local shattering to pieces and rebuilding of chromosomes in a random order. Congenital chromothripsis rearrangements often involve reciprocal rearrangements on multiple chromosomes and have been described as cause of contiguous gene syndromes. We hypothesize that chromothripsis could be responsible for known 9q21.13 microdeletion syndrome, causing a composite phenotype with additional features. CASE PRESENTATION: The case reported is a 16- years-old female with a complex genomic rearrangement of chromosome 9 including the critical region of 9q21.13 microdeletion syndrome. The patient presents with platelet disorder and thyroid dysfunction in addition to the classical neurobehavioral phenotype of the syndrome. CONCLUSIONS: The presence of multiple rearrangements on the same chromosome 9 and the rebuilding of chromosome in a random order suggested that the rearrangement could origin from an event of chromthripsis. To our knowledge this is the first report of congenital chromothripsis involving chromosome 9. Furthermore this is the only case of 9q21.13 microdeletion syndrome due to chromothripsis.

19.
Nat Immunol ; 16(11): 1174-84, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26414764

RESUMO

Human regulatory T cells (T(reg) cells) that develop from conventional T cells (T(conv) cells) following suboptimal stimulation via the T cell antigen receptor (TCR) (induced T(reg) cells (iT(reg) cells)) express the transcription factor Foxp3, are suppressive, and display an active proliferative and metabolic state. Here we found that the induction and suppressive function of iT(reg) cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3-E2-related suppressive activity of iT(reg) cells was altered in human autoimmune diseases, including multiple sclerosis and type 1 diabetes, and was associated with impaired glycolysis and signaling via interleukin 2. This link between glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown mechanism for controlling the induction and function of T(reg) cells in health and in autoimmunity.


Assuntos
Fatores de Transcrição Forkhead/genética , Glicólise/genética , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adulto , Processamento Alternativo , Autoimunidade , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos T CD4-Positivos/classificação , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Éxons , Ácidos Graxos/metabolismo , Feminino , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/metabolismo , Técnicas de Silenciamento de Genes , Variação Genética , Humanos , Técnicas In Vitro , Masculino , Metaboloma , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/metabolismo , Oxirredução , Fosfopiruvato Hidratase/antagonistas & inibidores , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais/imunologia , Linfócitos T Reguladores/classificação , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem
20.
Horm Res Paediatr ; 84(2): 139-44, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26138370

RESUMO

Diabetic ketoacidosis (DKA) may be associated with neurologic complications: the most common is cerebral edema while the risk of venous and arterial stroke is rare. There is a pathogenetic link between DKA, hypercoagulability and stroke, whose risk is underestimated by clinicians. Our cases present a wide spectrum of cerebral accidents during DKA, the first one being diffuse cerebral edema, the second one venous stroke after 5 days of DKA resolution, while the third one multifocal edema suspected to be extrapontine myelinolysis although without electrolyte imbalance. Our cases suggest that DKA requires very accurate treatment, particularly at an early age, and it can be complicated by cerebral accidents even with appropriate medical care.


Assuntos
Cetoacidose Diabética/complicações , Acidente Vascular Cerebral/etiologia , Edema Encefálico/etiologia , Criança , Cetoacidose Diabética/tratamento farmacológico , Progressão da Doença , Feminino , Hidratação , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Resultado do Tratamento
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