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1.
Mol Genet Metab ; 142(1): 108151, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522180

RESUMO

OBJECTIVE: The aim of this study is to present a series of case studies on the real-life use of pegvaliase in Italy in managing patients affected by phenylketonuria (PKU) and provide practical insight and support to healthcare professionals currently approaching and facing this novel enzyme substitution therapy. METHODS: A panel of 11 PKU experts from seven leading Italian treatment centers attended online virtual meetings with the aim of reviewing their clinical and practical experiences with pegvaliase based on occurred cases. In selecting the cases, specific consideration was given to the nationwide representation of the centers involved and to the number of patients with PKU managed. Cases were thoroughly reviewed, with comprehensive discussions enabling the identification of key take-home messages regarding pegvaliase therapy. RESULTS: The panel discussed 18 cases, 11 males and 7 females (age range 17-43 years). At the last follow-up (up to 111 weeks after pegvaliase initiation), 11 out of 18 patients (61%) reached Phe levels below 600 µmol/l. Outcomes varied significantly across cases. All cases underscore the potential of pegvaliase in reducing Phe levels, enhancing the quality of life, and promoting social skills and independence. Additionally, the cases highlight the challenges associated with pegvaliase therapy, including managing adverse events and ensuring patient motivation and adherence. CONCLUSION: This is the first report about the Italian experience of managing patients affected by PKU with pegvaliase. Given the limited real-world data on the use of pegvaliase in PKU management, this case series offers valuable insights into the practical implementation and management of pegvaliase therapy in this Country. Continued research and data collection will be crucial to confirm and progress with this treatment. Despite potential challenges, pegvaliase therapy represents a substantial promise in managing PKU in Italy. Patient education, personalized treatment approaches, and careful monitoring are important to ensure optimal patient outcomes.


Assuntos
Fenilalanina Amônia-Liase , Fenilalanina , Fenilcetonúrias , Humanos , Fenilcetonúrias/tratamento farmacológico , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Itália , Fenilalanina Amônia-Liase/uso terapêutico , Fenilalanina Amônia-Liase/efeitos adversos , Terapia de Reposição de Enzimas , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Qualidade de Vida , Resultado do Tratamento
2.
Crit Rev Food Sci Nutr ; : 1-15, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818634

RESUMO

This review systematically explores the pivotal role of food science and technology as a support for Phenylketonuria (PKU) dietary management. It delves into the genetic and metabolic underpinnings of PKU, highlighting the crucial need for stringent dietary regulation to manage phenylalanine levels and mitigate neurological complications. Through bibliometric analysis and current product evaluations, it identifies trends in PKU food research, emphasizing recent innovations in food formulations such as glycomacropeptide (GMP) supplements and higher appealing low-phenylalanine food products. Furthermore, it accentuates the sensory and consumer aspects of PKU dietary solutions, underscoring the importance of palatability for adherence. Notably, the review introduces 3D food printing as an emerging technology for creating personalized, nutrient-optimized, and sensory-appealing foods for PKU patients, offering a new horizon in dietary management. This comprehensive assessment underscores the dynamic interplay between nutritional science, food technology, and sensory evaluation in improving the quality of life for individuals with PKU.

3.
Am J Med Genet A ; 188(10): 3032-3040, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35876338

RESUMO

Hemizygous missense variants in the RPL10 gene encoding a ribosomal unit are responsible for an X-linked syndrome presenting with intellectual disability (ID), autism spectrum disorder, epilepsy, dysmorphic features, and multiple congenital anomalies. Among 15 individuals with RPL10-related disorder reported so far, only one patient had retinitis pigmentosa and microcephaly was observed in approximately half of the cases. By exome sequencing, three Italian and one Spanish male children, from three independent families, were found to carry the same hemizygous novel missense variant p.(Arg32Leu) in RPL10, inherited by their unaffected mother in all cases. The variant, not reported in gnomAD, is located in the 28S rRNA binding region, affecting an evolutionary conserved residue and predicted to disrupt the salt-bridge between Arg32 and Asp28. In addition to features consistent with RPL10-related disorder, all four boys had retinal degeneration and postnatal microcephaly. Pathogenic variants in genes responsible for inherited retinal degenerations were ruled out in all the probands. A novel missense RPL10 variant was detected in four probands with a recurrent phenotype including ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies. The presented individuals suggest that retinopathy and postnatal microcephaly are clinical clues of RPL10-related disorder, and at least the retinal defect might be more specific for the p.(Arg32Leu) RPL10 variant, suggesting a specific genotype/phenotype correlation.


Assuntos
Transtorno do Espectro Autista , Deficiência Intelectual , Microcefalia , Malformações do Sistema Nervoso , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Microcefalia/genética , Microcefalia/patologia , Fenótipo
4.
Immunology ; 149(4): 423-431, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27502741

RESUMO

Inflammatory conditions and oxidative stress have a crucial role in Down syndrome (DS). Emerging studies have also reported an altered lipid profile in the early stages of DS. Our previous works demonstrate that citrate pathway activation is required for oxygen radical production during inflammation. Here, we find up-regulation of the citrate pathway and down-regulation of carnitine/acylcarnitine carrier and carnitine palmitoyl-transferase 1 genes in cells from children with DS. Interestingly, when the citrate pathway is inhibited, we observe a reduction in oxygen radicals as well as in lipid peroxidation levels. Our preliminary findings provide evidence for a citrate pathway dysregulation, which could be related to some phenotypic traits of people with DS.


Assuntos
Proteínas de Transporte de Ânions/metabolismo , Carnitina Aciltransferases/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina/metabolismo , Ácido Cítrico/metabolismo , Síndrome de Down/metabolismo , Leucócitos/fisiologia , Proteínas Mitocondriais/metabolismo , Proteínas de Transporte de Ânions/genética , Carnitina Aciltransferases/genética , Carnitina O-Palmitoiltransferase/genética , Linhagem Celular Transformada , Pré-Escolar , Síndrome de Down/genética , Síndrome de Down/imunologia , Regulação da Expressão Gênica , Humanos , Peroxidação de Lipídeos , Proteínas Mitocondriais/genética , Transportadores de Ânions Orgânicos , Estresse Oxidativo , Fenótipo , Característica Quantitativa Herdável
5.
Cancer Cell Int ; 15: 50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25983658

RESUMO

BACKGROUND: Despite the clinical response of conventional anticancer therapy, including chemotherapeutic treatments, radiation therapy and corticosteroids, tumorigenic B-cell lymphomas show an incomplete response to clinical practices that result in a minimal residual disease (MRD) where few residual neoplastic cells undetected in vivo, replenish the cancer cell reservoir. This scenario, which is also shared with other cancer diseases, requires the development of strategies to advance in novel, selective targeting toward the tumorigenic cells that survive to the anticancer agents. METHODS: Here, we have taken advantage of the therapeutic properties of an idiotype specific peptide (pA20-36) that bind specifically to murine B-lymphoma cells in the setting of an anti cancer strategy, based on the selected delivery of electrostatic-based complex, peptide-siRNA. To this end, two engineered, arginine rich, peptides that included the pA20-36 targeting sequence were designed to bind fluorescent-labelled siRNA. One peptide presented 9 Arg at the C-terminal of pA20-36 whereas the other included 5 Arg at the N- and C-terminus, respectively. RESULTS: Compared to the control and random peptide-siRNA complexes, both pA20-36-siRNA complexes were endowed with the selective delivering of fluorescent-labelled siRNA toward the A20 murine B-cell lymphoma, as evaluated by cytofluorimetry and confocal microscopy, whereas fluorescent-labelled siRNA alone was not internalized in the selected cells. Compared to peptide controls, the use of the modified pA20-36 peptides complexed with siRNA anti-GAPDH and anti-Bcl2 showed a down-regulation in the expression levels of the corresponding genes. CONCLUSIONS: Peptide-siRNA complex can be suitable tool for both selective peptide-driven cell targeting and gene silencing. In this setting, the improvement of this strategy is expected to provide a safe and non-invasive approach for the delivery of therapeutic molecules.

6.
Biochim Biophys Acta ; 1832(4): 542-52, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23291000

RESUMO

A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria. In this study we have tested the potential of epigallocatechin-3-gallate (EGCG) - a natural polyphenol component of green tea - to counteract the mitochondrial energy deficit found in DS cells. We found that EGCG, incubated with cultured lymphoblasts and fibroblasts from DS subjects, rescued mitochondrial complex I and ATP synthase catalytic activities, restored oxidative phosphorylation efficiency and counteracted oxidative stress. These effects were associated with EGCG-induced promotion of PKA activity, related to increased cellular levels of cAMP and PKA-dependent phosphorylation of the NDUFS4 subunit of complex I. In addition, EGCG strongly promoted mitochondrial biogenesis in DS cells, as associated with increase in Sirt1-dependent PGC-1α deacetylation, NRF-1 and T-FAM protein levels and mitochondrial DNA content. In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS.


Assuntos
Trifosfato de Adenosina/biossíntese , Catequina/análogos & derivados , Síndrome de Down , Mitocôndrias , Catequina/farmacologia , Células Cultivadas , Cromossomos Humanos Par 21 , Síndrome de Down/genética , Síndrome de Down/fisiopatologia , Fibroblastos/efeitos dos fármacos , Proteínas de Choque Térmico/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Chá/química , Fatores de Transcrição/metabolismo , Trissomia
7.
Mol Genet Metab Rep ; 39: 101065, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38425869

RESUMO

Objective: Phenylketonuria (PKU) is a metabolic disorder necessitating lifelong management to prevent severe neurological impairments. This paper synthesises clinical practices from Italian specialist centres to delineate a unified approach for administering pegvaliase, a novel enzyme replacement therapy for PKU. Methods: Virtual meetings convened in September 2022, gathering a steering committee (SC) of experts from five Italian centres specialising in PKU. The SC reviewed, and discussed clinical practices, and formulated recommendations for pegvaliase treatment. Results: The SC outlined a comprehensive treatment roadmap for PKU management with pegvaliase, emphasising the importance of multidisciplinary care teams, patient selection, pre-treatment evaluation, and education. Recommendations include initial hospital-based pegvaliase administration, regular monitoring of phenylalanine and tyrosine levels, dietary adjustments, and management of adverse events. A consensus was reached on the need for a digital database to manage treatment plans and enhance communication between healthcare professionals and patients. Conclusion: The expert panel's consensus highlights the complexity of PKU management and the necessity for a coordinated, patient-centred approach. The recommendations aim to standardise care across Italian centres and provide a framework for integrating pegvaliase therapy into clinical practice, potentially informing international guidelines. Further research is warranted to evaluate the long-term impact of these practices on patient outcomes and quality of life.

8.
Acta Neurol Belg ; 124(1): 223-230, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37733157

RESUMO

PURPOSE: Cognitive impairment is described in 80% of Neurofibromatosis type 1 (NF1) patients. Brain focal areas of T2w increased signal intensity on MRI, the so-called Unidentified Bright Objects (UBOs) have been hypothesized to be related to cognitive dysfunction, although conflicting results are available in literature. Here, we investigated the possible relation between UBOs' volume, cognitive impairment, and language disability in NF1 patients. MATERIAL AND METHODS: In this retrospective study, clinical and MRI data of 21 NF1 patients (M/F = 12/9; mean age 10.1 ± 4.5) were evaluated. Brain intellectual functioning and language abilities were assessed with specific scales, while the analyzed MRI sequences included axial 2D-T2-weighted and FLAIR sequences. These images were used independently for UBOs segmentation with a semiautomatic approach and obtained volumes were normalized for biparietal diameters to take into account for brain volume. Possible differences in terms of normalized UBOs volumes were probed between cognitively affected and preserved patients, as well as between subjects with or without language impairment. RESULTS: Patients cognitively affected were not different in terms of UBOs volume compared to those preserved (p = 0.35 and p = 0.30, for T2-weighted and FLAIR images, respectively). Similarly, no differences were found between patients with and without language impairment (p = 0.47 and p = 0.40, for the two sequences). CONCLUSIONS: The relation between UBOs and cognition in children with NF1 has been already investigated in literature, although leading to conflicting results. Our study expands the current knowledge, showing a lack of correlation between UBOs volume and both cognitive impairment and language disability in NF1 patients.


Assuntos
Transtornos do Desenvolvimento da Linguagem , Neurofibromatose 1 , Criança , Humanos , Pré-Escolar , Adolescente , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Cognição
9.
Neurosci Biobehav Rev ; 149: 105156, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37019246

RESUMO

Children and adolescents with neurodevelopmental disorders generally show adaptive, cognitive and motor skills impairments associated with behavioral problems, i.e., alterations in attention, anxiety and stress regulation, emotional and social relationships, which strongly limit their quality of life. This narrative review aims at providing a critical overview of the current knowledge in the field of serious games (SGs), known as digital instructional interactive videogames, applied to neurodevelopmental disorders. Indeed, a growing number of studies is drawing attention to SGs as innovative and promising interventions in managing neurobehavioral and cognitive disturbs in children with neurodevelopmental disorders. Accordingly, we provide a literature overview of the current evidence regarding the actions and the effects of SGs. In addition, we describe neurobehavioral alterations occurring in some specific neurodevelopmental disorders for which a possible therapeutic use of SGs has been suggested. Finally, we discuss findings obtained in clinical trials using SGs as digital therapeutics in neurodevelopment disorders and suggest new directions and hypotheses for future studies to bridge the gaps between clinical research and clinical practice.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Criança , Adolescente , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Qualidade de Vida , Transtornos do Neurodesenvolvimento/terapia , Relações Interpessoais , Ansiedade
10.
Minerva Pediatr (Torino) ; 74(1): 31-39, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-29460553

RESUMO

BACKGROUND: The development of both gross and fine motor skills in a child with Down syndrome is generally delayed. The most seriously affected stage is the achievement of independent walking ability, which influences the onset of all following motor and cognitive skills. The study objectives were: 1) to assess the time taken to achieve independent walking ability in a cohort of children with Down syndrome; 2) to examine differences in walking onset by patient characteristics; and 3) to verify the effect of early physical therapy (neurodevelopmental treatment based on Bobath Concept practiced within the first months of life) in the achievement of that skill. METHODS: A retrospective study was carried out on a cohort of 86 children with Down Syndrome. The knowledge of the exact age of walking onset and information about comorbidities and rehabilitation practiced since birth were the eligibility criteria. RESULTS: The average age at which walking began in the sample was 26 months (standard deviation=9.66). Some patient characteristics proved to be related negatively to the walking onset: gender male, trisomy 21, improved joint ligamentous laxity. When practiced, early physical therapy was able to contrast the delay in walking. CONCLUSIONS: NDT-Bobath is a well-known and valid instrument for a child with Down syndrome to attain his highest possible psychomotor functioning level. This study pointed out for the first time ever its capability to contrast the delay on walking onset, which can influence positively the development of the following motor and cognitive skills.


Assuntos
Síndrome de Down , Estudos de Coortes , Síndrome de Down/reabilitação , Humanos , Lactente , Masculino , Modalidades de Fisioterapia , Estudos Retrospectivos , Caminhada
11.
J Pers Med ; 13(1)2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36675732

RESUMO

A comprehensive evaluation of obstructive sleep apnoea (OSA) may allow for the development of more efficient management of Down syndrome (DS). We aimed to evaluate the effect of a multidisciplinary approach to DS with OSA. A total of 48 DS children aged 4−12 years were prospectively investigated with nasal endoscopy, orthodontic examination, and overnight polygraphy (PG); the Italian Child Sleep Habits Questionnaire (CSHQ-IT) was filled out by the mothers. The total CSHQ-IT score was 63 (96% of children reporting sleep problems). The major ear, nose, and throat characteristics were enlarged palatine tonsils (62%), adenoid tonsils (85%), and chronic rhinosinusitis (85%). DS children showed orthognathic profile in 68% of cases, class I relationship in 63%, and cross-bite in 51%. PG revealed OSA in 67% of cases (37% mild, 63% moderate−severe). The oxygen desaturation index (ODI) was higher in the group with OSA (5.2) than with non-OSA (1.3; p < 0.001). The ODI was higher (p = 0.001) and SpO2 lower (p = 0.03) in children with moderate−severe OSA than with mild OSA. The apnoea−hypopnea index (AHI) and percentage time with SpO2 < 90% were higher in DS children with grade III than with grade I or II adenoids (5 vs. 1, p = 0.04, and 1.2 vs. 0.1, p = 0.01, respectively). No significant correlations were found between PG and the total CSHQ-IT score or orthodontic data. However, children showing associated cross-bite, grade III adenoids and size 3 or 4 palatine tonsils showed higher AHI and ODI than those without (p = 0.01 and p = 0.04, respectively). A coordinated multidisciplinary approach with overnight PG is a valuable tool when developing diagnostic protocols for OSA in DS.

12.
Mol Genet Metab ; 102(3): 378-82, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21195648

RESUMO

In Down's syndrome there is evidence that increased gene expression coding for specific cystathionine beta-synthase translates directly into biochemical aberrations, which result in a biochemical and metabolic imbalance of the methyl status. This event is destined to impact mitochondrial function since methylation is a necessary event in mitochondria and relies on the availability and uptake of the methyl donor S-adenosylmethionine. Indeed mitochondrial dysfunctions have been widely described in Down's syndrome, but they have never been correlated to a possible mitochondrial methyl unbalance. In the present study we find that the mitochondrial levels of S-adenosylmethionine are reduced in Down's syndrome compared to control cells demonstrating the effect of the methyl unbalance on mitochondria. The possible role of methylation in mitochondria is discussed and some preliminary results on a possible methylation target are presented.


Assuntos
Síndrome de Down/fisiopatologia , Glutationa/metabolismo , Mitocôndrias/metabolismo , Adolescente , Proteínas de Transporte/genética , Linhagem Celular Transformada , Criança , Pré-Escolar , Citosol/metabolismo , Síndrome de Down/genética , Síndrome de Down/metabolismo , Humanos , Lactente , Metilação , Mitocôndrias/genética , S-Adenosilmetionina/metabolismo
13.
Ital J Pediatr ; 47(1): 148, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215294

RESUMO

BACKGROUND: White-Sutton (WHSUS) is a recently recognized syndrome caused by mutations of the POGZ gene. Approximately 70 patients have been reported to date. Intellectual disability, hypotonia, behavioral abnormalities, autism, and typical facial dysmorphisms are recognized as WHSUS features; however, still few patients receive a comprehensive psychometric, behavioral and neurological examination. In this report, we describe the pediatric, dysmorphological, neurological, psychometric and behavioral phenotype in a new WHSUS patient due to a novel heterozygous POGZ mutation, highlighting the distinctive epileptic phenotype and the cognitive pattern. CASE PRESENTATION: The patient, an 8 years-old girl, presented history of hypotonia, motor and speech delay, and distinctive facial features. The diagnosis of WHSUS followed the identification of the de novo variant p.Asp828GlyfsTer36 (c.2482dupG) in the POGZ gene. The patient showed a distinctive neurological phenotype with the occurrence of both paroxysmal not-epileptic events in the first 6 months of age and EEG abnormalities without evidence of clinical seizures after the first year of age. Psychological and behavioral testing highlighted moderate intellectual and communication deficit, mild autism spectrum and visual-motor integration deficit. CONCLUSIONS: This is the first described case of WHSUS with a co-existence of paroxysmal not-epileptic events and abnormal EEG without seizures in the same patient. Together with the available literature data, this observation suggests that paroxysmal not-epileptic events could be more frequent than expected and that this feature belongs to the WHSUS phenotypic spectrum. Autism is a known comorbidity of WHSUS but is still poorly investigated. Specific clinical testing could help detect also mild autistic phenotypes and better define autism prevalence in POGZ-related syndrome. Special attention should be given to symptoms such as stereotypies, social withdrawal, and hyperactivity that, when present, should be considered as possible signs of autism symptoms. The dissection of the neurological and behavioral phenotype is crucial for individualized therapies tailored to patient's needs.


Assuntos
Transtorno Autístico/genética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual/genética , Criança , Eletroencefalografia , Feminino , Humanos , Mutação , Fenótipo , Síndrome
14.
Antioxidants (Basel) ; 10(3)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33809669

RESUMO

Down syndrome (DS) is a major genetic cause of intellectual disability. DS pathogenesis has not been fully elucidated, and no specific pharmacological therapy is available. DYRK1A overexpression, oxidative stress and mitochondrial dysfunction were described in trisomy 21. Epigallocatechin-3-gallate (EGCG) is a multimodal nutraceutical with antioxidant properties. EGCG inhibits DYRK1A overexpression and corrects DS mitochondrial dysfunction in vitro. The present study explores safety profiles in DS children aged 1-8 years treated with EGCG (10 mg/kg/die, suspended in omega-3, per os, in fasting conditions, for 6 months) and EGCG efficacy in restoring mitochondrial complex I and F0F1-ATP synthase (complex V) deficiency, assessed on PBMCs. The Griffiths Mental Developmental Scales-Extended Revised (GMDS-ER) was used for developmental profiling. Results show that decaffeinated EGCG (>90%) plus omega-3 is safe in DS children and effective in reverting the deficit of mitochondrial complex I and V activities. Decline of plasma folates was observed in 21% of EGCG-treated patients and should be carefully monitored. GMDS-ER scores did not show differences between the treated group compared to the DS control group. In conclusion, EGCG plus omega-3 can be safely administered under medical supervision in DS children aged 1-8 years to normalize mitochondria respiratory chain complex activities, while results on the improvement of developmental performance are still inconclusive.

15.
Nutrients ; 13(11)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34836270

RESUMO

The mainstay of phenylketonuria treatment is a low protein diet, supplemented with phenylalanine (Phe)-free protein substitutes and micronutrients. Adhering to this diet is challenging, and even patients with good metabolic control who follow the dietary prescriptions in everyday life ignore the recommendations occasionally. The present study explores the ability of slow-release large neutral amino acids (srLNAAs) to prevent Phe increase following a Phe dietary load. Fourteen phenylketonuric patients aged ≥13 years were enrolled in a 6-week protocol. Oral acute Phe loads of 250 and 500 mg were added to the evening meal together with srLNAAs (0.5 gr/kg). Phe and tyrosine were dosed before dinner, 2h-after dinner, and after the overnight fast. After oral Phe loads, mean plasma Phe remained stable and below 600 µmol/L. No Phe peaks were registered. Tyrosine levels significantly increased, and Phe/Tyrosine ratio decreased. No adverse events were registered. In conclusion, a single oral administration of srLNAAs at the dose of 0.5 gr/kg is effective in maintaining stable plasma Phe during acute oral loads with Phe-containing food and may be added to the dietetic scheme in situations in which patients with generally good adherence to diet foresee a higher than prescribed Phe intake due to their commitments.


Assuntos
Aminoácidos Neutros/administração & dosagem , Suplementos Nutricionais , Fenilalanina/administração & dosagem , Fenilcetonúrias/tratamento farmacológico , Adolescente , Adulto , Aminoácidos/administração & dosagem , Aminoácidos Neutros/sangue , Aminoácidos Neutros/uso terapêutico , Dieta , Feminino , Humanos , Itália , Masculino , Micronutrientes/uso terapêutico , Fenilalanina/sangue , Fenilalanina/uso terapêutico , Fenilcetonúrias/sangue , Tirosina/sangue , Tirosina/uso terapêutico , Adulto Jovem
16.
Ital J Pediatr ; 47(1): 170, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372910

RESUMO

BACKGROUND: The Children's Sleep Habits Questionnaire (CSHQ) is a parent-report questionnaire used to examine sleep behavior in children. Linguistic adaptation of CSHQ into several languages and/or psychometric analysis of reliability have been published. MAIN TEXT: Our aim was to translate the original 33-items CSHQ from English to Italian and to examine its reliability for use in 4-10 years-old children of Italy. After translation and back-translation procedure of the original CSHQ, the Italian CSHQ (CSHQ-IT) was administered to 69 mothers of healthy children. Reliability of CSHQ-IT was examined by the internal consistency of the scale (using the Cronbach's alpha coefficient), and by the test-retest analysis obtained by asking mothers who had completed the CSHQ-IT at baseline to re-complete it after a two-week interval (measured with the Lin's Concordance Correlation Coefficient, CCC). The CSHQ-IT showed adequate internal consistency (Cronbach's alpha = 0.81 for the total scale). The total CSHQ-IT score showed a strong correlation in retests (CCC 0.87; 95% Confidence Interval, 0.80; 0.92). CONCLUSION: CSHQ-IT is a valuable tool for evaluating sleep behavior in children 4-10 years-old in Italy. Future research should be implemented to provide definitive validity of CSHQ-IT in children with sleep-disordered breathing.


Assuntos
Sono , Inquéritos e Questionários , Criança , Pré-Escolar , Humanos , Itália , Idioma , Psicometria , Reprodutibilidade dos Testes , Traduções
17.
Nutrients ; 12(4)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32326614

RESUMO

Phenylketonuria is an inborn error of phenylalanine (Phe) metabolism diagnosed by newborn screening and treated early with diet. Although diet prevents intellectual disability, patients often show impairment of executive functions, working memory, sustained attention, and cognitive flexibility. Large neutral amino acids (LNAAs) have been proposed as a dietary supplement for PKU adults. Few studies show that LNAAs may help in improving metabolic control as well as cognitive functions. In this study, 10 adult PKU patients with poor metabolic control were treated for 12 months with LNAAs (MovisCom, 0.8-1 g/kg/day) and underwent Phe and Tyrosine (Tyr) monitoring monthly. Neuropsychological assessment was performed at T0, T+3, and T+12 months by using the American Psychological General Well-Being Index, the Wisconsin Card Sorting Test, the Test of Attentional Performance, and the 9-Hole Peg Test. No change in plasma Phe levels was observed during LNAAs supplementation, while Tyr levels significantly improved during LNAAs supplementation (p = 0.03). Psychometric tests showed an improvement of distress and well-being rates, of executive functions, attention, and vigilance, whereas no difference was noted regarding hand dexterity. This study adds evidence of the advantage of LNAAs supplementation in improving cognitive functions and well-being in patients with PKU with poor metabolic control.


Assuntos
Aminoácidos Neutros/administração & dosagem , Aminoácidos Neutros/farmacologia , Atenção , Encéfalo/fisiopatologia , Cognição , Suplementos Nutricionais , Função Executiva , Memória de Curto Prazo , Testes Neuropsicológicos , Fenilcetonúrias/dietoterapia , Fenilcetonúrias/psicologia , Adolescente , Adulto , Nível de Alerta , Feminino , Humanos , Masculino , Fenilalanina/sangue , Fenilcetonúrias/metabolismo , Resultado do Tratamento , Adulto Jovem
18.
Eur J Endocrinol ; 182(4): 385-392, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31999620

RESUMO

OBJECTIVE: To evaluate the prevalence and natural course of autoimmune and non-autoimmune subclinical hypothyroidism (SH) in Down syndrome (DS) children and adolescents. DESIGN: Prospective multicenter study. METHODS: For the study, 101 DS patients with SH (TSH 5-10 mIU/L; FT4 12-22 pmol/L), aged 2-17 years at SH diagnosis were enrolled. Annual monitoring of TSH, FT4, BMI, height, and L-thyroxine dose was recorded for 5 years. Thyroid autoimmunity was tested at diagnosis and at the end of follow-up. RESULTS: Thirty-seven out of 101 patients displayed autoantibody positivity (group A); the remaining 64 were classified as non-autoimmune SH (group B). Group A was characterized by higher median age at SH diagnosis and by more frequent family history of thyroid disease (6.6 vs 4.7 years, P = 0.001; 32.4% vs 7.8%, P = 0.001 respectively), whereas congenital heart defects were more common in group B (65.6% vs 43.2%, P = 0.028). Gender, median BMI (SDS), height (SDS), FT4, and TSH were similar in both groups. At the end of follow-up: 35.1% of group A patients developed overt hypothyroidism (OH) vs 17.2% of group B (P = 0.041); 31.25% of group B vs 10.8% of group A became biochemically euthyroid (P = 0.02); and 37.8% of group A vs 51.5% of group B still had SH condition (P = 0.183). Logistic regression suggested autoimmunity (OR = 3.2) and baseline TSH values (OR = 1.13) as predictive factors of the evolution from SH to OH. CONCLUSIONS: In DS children, non-autoimmune SH showed higher prevalence and earlier onset. The risk of thyroid function deterioration over time seems to be influenced by thyroid autoimmunity and higher baseline TSH values.


Assuntos
Síndrome de Down/epidemiologia , Doença de Hashimoto/epidemiologia , Tireoidite Autoimune/epidemiologia , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Síndrome de Down/complicações , Feminino , Doença de Hashimoto/complicações , Humanos , Masculino , Estudos Prospectivos , Tireoidite Autoimune/complicações
19.
FEBS J ; 274(20): 5263-77, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17892495

RESUMO

Spontaneous protein deamidation of labile Asn residues, generating L-isoaspartates and D-aspartates, is associated with cell aging and is enhanced by an oxidative microenvironment; to minimize the damage, the isoaspartate residues can be 'repaired' by a specific L-isoaspartate (D-aspartate) protein O-methyltransferase (PIMT). As both premature aging and chronic oxidative stress are typical features of Down's syndrome (DS), we tested the hypothesis that deamidated proteins may build up in trisomic patients. Blood samples were obtained from children with karyotypically confirmed full trisomy 21 and from age-matched healthy controls. Using recombinant PIMT as a probe, we demonstrated a dramatic rise of L-isoaspartates in erythrocyte membrane proteins from DS patients. The content of D-aspartate was also significantly increased. The integrity of the repair system was checked by evaluating methionine transport, PIMT specific activity, and intracellular concentrations of adenosylmethionine and adenosylhomocysteine. The overall methylation pathway was directly monitored by incubating fresh red blood cells with methyl-labeled methionine; a three-fold increase of protein methyl esters was detected in trisomic children. Deamidated species include ankyrin, band 4.1, band 4.2 and the integral membrane protein band 3; ankyrin and band 4.1 were significantly hypermethylated in DS. When DS red blood cells were subjected to oxidative treatment in vitro, the increase of protein deamidation paralleled lipid peroxidation and free radical generation. We observed a similar pattern in Epstein-Barr virus B-lymphocytes from trisomic patients. In conclusion, our findings support the hypothesis that protein instability at asparagine sites is a biochemical feature of DS, presumably depending upon the oxidative microenvironment. The possible pathophysiological implications are discussed.


Assuntos
Síndrome de Down/sangue , Membrana Eritrocítica/metabolismo , Ácido Isoaspártico/metabolismo , Proteínas de Membrana/metabolismo , Estudos de Casos e Controles , Criança , Síndrome de Down/patologia , Envelhecimento Eritrocítico , Herpesvirus Humano 4/fisiologia , Humanos , Linfócitos/citologia , Linfócitos/metabolismo , Linfócitos/virologia , Metemoglobina/metabolismo , Metionina/metabolismo , Metilação , Estresse Oxidativo , Proteína D-Aspartato-L-Isoaspartato Metiltransferase/metabolismo , Proteínas Recombinantes/metabolismo , S-Adenosil-Homocisteína/metabolismo
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