Journal of pediatric biochemistry最新文献_第4页

Journal of pediatric biochemistry Pub Date : 2016-03-01 DOI: 10.1055/s-0036-1582253

S. Sestito, F. Falvo, M. Grisolia, A. Nicoletti, E. Pascale, M. Moricca, S. Esposito, V. Salpietro, A. Polizzi, M. Ruggieri, D. Concolino

{"title":"Neuronopathic Gaucher Disease","authors":"S. Sestito, F. Falvo, M. Grisolia, A. Nicoletti, E. Pascale, M. Moricca, S. Esposito, V. Salpietro, A. Polizzi, M. Ruggieri, D. Concolino","doi":"10.1055/s-0036-1582253","DOIUrl":"https://doi.org/10.1055/s-0036-1582253","url":null,"abstract":"Abstract Gaucher disease (GD) has been classically divided into three phenotypes primarily according to the absence (type 1 GD or nonneuronopathic GD) or presence and severity (types 2 and 3 GD or neuronopathic GD) of neurological involvement. Despite such distinction, neurological manifestations have been recorded also in patients with type 1 GD: in this latter form, however, such manifestations are different and, in the majority of cases, of much less severity than those associated with types 2 and 3 GD. Significant advances in therapy have been achieved, primarily after the advent of enzyme replacement therapy (ERT). As it occurs in patients with type 1 GD, ERT is able to reverse systemic and extraneurological manifestations of type 3 GD, although evidence suggests that ERT is not able to prevent the progression of neurological involvement in the long term. Thus, it is necessary to better understand the pathophysiological mechanism underlying neurological involvement in GD patients, allowing the development of new therapeutic approaches capable of improving central nervous system manifestations in GD.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"039 - 045"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Pathobiological Insights into Neurological Involvement in Cobalamin C Deficiency 钴胺素C缺乏与神经系统相关的病理生物学研究

Journal of pediatric biochemistry Pub Date : 2016-03-01 DOI: 10.1055/s-0036-1582251

Ferdinando Ceravolo, M. Grisolia, Angela Nicolettti, S. Sestito, V. Salpietro, A. Polizzi, M. Ruggieri, G. Bonapace, E. Pascale, D. Concolino

{"title":"Pathobiological Insights into Neurological Involvement in Cobalamin C Deficiency","authors":"Ferdinando Ceravolo, M. Grisolia, Angela Nicolettti, S. Sestito, V. Salpietro, A. Polizzi, M. Ruggieri, G. Bonapace, E. Pascale, D. Concolino","doi":"10.1055/s-0036-1582251","DOIUrl":"https://doi.org/10.1055/s-0036-1582251","url":null,"abstract":"Abstract Cobalamin C (Cbl-C) defects are inherited autosomal recessive disorders of vitamin B12 (or cyanocobalamin [CNCbl]) metabolism. These defects are caused by mutations in the methylmalonic aciduria and homocystinuria Cbl-C type (MMACHC; MIM # 609831) gene located on chromosome 1p34.1, which catalyzes the reductive decyanation of CNCbl, thus impairing the biosynthesis of 5′-deoxyadenosylcobalamin, adenosylcobalamin, and methylcobalamin. This impairment results in methylmalonic acidemia [MMA; MIM # 277400] combined with hyperhomocysteinemia and hypomethioninemia. Clinically, Cbl-C defects are characterized by a constellation of systemic signs and symptoms, including neurological, cognitive, psychiatric, and thromboembolic events. Retinal phenotypes, including maculopathy, pigmentary retinopathy, and optic atrophy, are common in the early-onset form of the disease, but are rare in its adult-onset counterpart. Administration of hydroxocobalamin (OHCbl), betaine, and folinic acid represents main therapeutic approaches. No proven efficacy has been demonstrated for carnitine and dietary protein restrictions. Although early introduction of OHCbl is crucial, no standardized protocols regarding dose adjustment exist. Despite these measures, the long-term outcome is unsatisfactory especially in patients with early onset, who experience frequent progression of their neurological and ocular impairment. The unfavorable outcome suggests that a better understanding of the pathophysiology of the disease is needed to improve treatment protocols and to develop new therapeutic approaches.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"025 - 029"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathobiological Insights into the Newly Targeted Therapies of Lysosomal Storage Disorders 溶酶体贮积症新靶向治疗的病理生物学见解

Journal of pediatric biochemistry Pub Date : 2016-03-01 DOI: 10.1055/s-0036-1582224

S. Sestito, Ferdinando Ceravolo, F. Falvo, A. Nicoletti, E. Stefanelli, R. Apa, V. Salpietro, A. Polizzi, M. Ruggieri, D. Concolino

{"title":"Pathobiological Insights into the Newly Targeted Therapies of Lysosomal Storage Disorders","authors":"S. Sestito, Ferdinando Ceravolo, F. Falvo, A. Nicoletti, E. Stefanelli, R. Apa, V. Salpietro, A. Polizzi, M. Ruggieri, D. Concolino","doi":"10.1055/s-0036-1582224","DOIUrl":"https://doi.org/10.1055/s-0036-1582224","url":null,"abstract":"Abstract Lysosomal storage disorders (LSDs) are a heterogeneous group of inborn errors of metabolism caused by inherited deficiencies of any of the lysosomal functions, leading to the accumulation of undegraded substrates in multiple tissues and organs. Two-third of LSDs involves the central nervous system, thus representing the most common cause of pediatric neurodegenerative diseases. Substantial progress has been made in our understanding of the pathophysiology of LSDs, leading to newly targeted therapeutic options. Enzyme replacement therapy (ERT) is currently available for seven LSDs including Gaucher disease, Fabry disease, Pompe disease, and mucopolysaccharidosis (MPS) I (Hurler disease), II (Hunter disease), IV A (Morquio A), and VI (Maroteaux–Lamy disease). ERT reduces lysosomal storage, thus slowing or sometimes avoiding progressive visceral damage altogether. However, ERT is unable to cross the blood–brain barrier (BBB), thus lacking efficacy on neurological manifestations. In patients with MPS I (Hurler disease) under 2 years of age and in selected patients with other LSD, hematopoietic stem cell transplantation is indicated. To bypass the BBB, other approaches, using small molecules are currently being tested and include substrate reduction therapy, which decreases the amount of substrate (currently available for type 1 Gaucher disease and for Niemann–Pick type C disease) and pharmacological chaperones, which enhance the residual activity of the mutant enzyme.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"030 - 038"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582224","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Hyperphenylalaninemia: From Diagnosis to Therapy 高苯丙氨酸血症:从诊断到治疗

Journal of pediatric biochemistry Pub Date : 2016-03-01 DOI: 10.1055/s-0036-1582237

D. Procópio, I. Mascaro, S. Ferraro, Ferdinando Ceravolo, M. Moricca, V. Salpietro, A. Polizzi, M. Ruggieri, G. Bonapace, D. Concolino

{"title":"Hyperphenylalaninemia: From Diagnosis to Therapy","authors":"D. Procópio, I. Mascaro, S. Ferraro, Ferdinando Ceravolo, M. Moricca, V. Salpietro, A. Polizzi, M. Ruggieri, G. Bonapace, D. Concolino","doi":"10.1055/s-0036-1582237","DOIUrl":"https://doi.org/10.1055/s-0036-1582237","url":null,"abstract":"Abstract Hyperphenylalaninemia (HPA) is a biochemical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine (Phe) in the blood. HPA is commonly diagnosed by newborn screening. The primary cause of HPA is phenylketonuria (PKU), an inborn error of metabolism characterized by persistently elevated plasma concentrations of Phe secondary to a total or partial deficiency of the liver enzyme phenylalanine hydroxylase. The treatment of babies affected with PKU is based on a Phe-restricted diet, aiming to maintain blood Phe concentrations within a range of 120 to 360 μmol/L to prevent the spectrum of neurological disorders associated with PKU, that is, microcephaly, learning disability, epilepsy, pyramidal and extrapyramidal signs, and behavioral changes. This metabolic disorder mainly affects the white matter (e.g., dysmyelination, demyelination, and hypomyelination) and the cortical-subcortical structures. A delay in starting the dietary treatment, or an inadequate Phe-restricted diet, may relentlessly lead to brain damage.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"06 1","pages":"011 - 018"},"PeriodicalIF":0.0,"publicationDate":"2016-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1582237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58141521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The Neuronal Ceroid Lipofuscinoses: A Case-Based Overview 神经元类脂褐细胞病:基于病例的综述

Journal of pediatric biochemistry Pub Date : 2016-01-18 DOI: 10.1055/s-0036-1582222

M. Grisolia, S. Sestito, Ferdinando Ceravolo, F. Invernizzi, V. Salpietro, A. Polizzi, M. Ruggieri, B. Garavaglia, D. Concolino

引用次数: 4

Neuroblastoma: Diagnostic and Clinical Aspects 神经母细胞瘤:诊断和临床方面

Journal of pediatric biochemistry Pub Date : 2015-12-01 DOI: 10.1055/s-0036-1572525

S. Marino, F. Puglisi, G. Magro, G. Belfiore, V. Di Benedetto, M. Scuderi, A. Portale, S. D’amico, V. Miraglia, M. Licciardello, L. Lo Nigro, M. La Spina, G. Russo, A. Di Cataldo

{"title":"Neuroblastoma: Diagnostic and Clinical Aspects","authors":"S. Marino, F. Puglisi, G. Magro, G. Belfiore, V. Di Benedetto, M. Scuderi, A. Portale, S. D’amico, V. Miraglia, M. Licciardello, L. Lo Nigro, M. La Spina, G. Russo, A. Di Cataldo","doi":"10.1055/s-0036-1572525","DOIUrl":"https://doi.org/10.1055/s-0036-1572525","url":null,"abstract":"Abstract Due to its many clinical and biologic characteristics, neuroblastoma (NB) is a polyhedric neoplasm. It is a very complex, extremely heterogeneous disease that can regress spontaneously even without therapy. However, it frequently shows a very aggressive behavior, refractory to current intensive multimodal therapy. The tumor, originating from primordial neural crest cells, is biochemically unique for its metabolic pathways of catecholamine synthesis and metabolism. Homovanillic acid (HVA), the main metabolite of dopamine, and vanillylmandelic acid (VMA), the main metabolite of adrenalin and noradrenalin, are sensitive and convenient markers of NB since they are found in large amounts in patient's urine. The rate of NB patients with positive VMA and/or HVA at the diagnosis varies with the stage of the disease, with high-stage tumors being more likely to have abnormal levels. Other less specific NB tumor serum markers are neuron-specific enolase, ferritin, and lactate dehydrogenase. NB is one of the few pediatric tumors in which tumor markers have been shown to have a role in the diagnosis, prognosis, and disease monitoring.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"05 1","pages":"131 - 138"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1572525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58128200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Cell Manipulation in Pediatric Haploidentical Stem Cell Transplantation: State of the Art 儿童单倍体干细胞移植中的细胞操作:最新进展

Journal of pediatric biochemistry Pub Date : 2015-12-01 DOI: 10.1055/s-0036-1572322

M. Tumino, A. Marzollo, M. Gazzola, E. Calore, C. Mainardi, M. Pillon, R. Destro, M. Gabelli, A. Strano, M. Barioni, C. Messina

{"title":"Cell Manipulation in Pediatric Haploidentical Stem Cell Transplantation: State of the Art","authors":"M. Tumino, A. Marzollo, M. Gazzola, E. Calore, C. Mainardi, M. Pillon, R. Destro, M. Gabelli, A. Strano, M. Barioni, C. Messina","doi":"10.1055/s-0036-1572322","DOIUrl":"https://doi.org/10.1055/s-0036-1572322","url":null,"abstract":"Abstract Haploidentical transplantation in children can extend the opportunity for transplantation to almost every patient lacking a human leukocyte antigen (HLA)–matched donor and offer this treatment to every child with an otherwise incurable disease. Although initial attempts were associated with a high transplant-related mortality, recent insights into the biology of haploidentical transplantation, the availability of effective ex vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to significantly better outcomes. Concurrently, the indication for haploidentical transplantation has been extended, including different malignant and nonmalignant conditions. Worldwide donor registries include mainly donors of Caucasian origin. Patients of non-Caucasian origin have a lower chance of finding a suitable unrelated donor. Haploidentical transplantation allows the treatment of children independently of their ethnic background in a timely fashion. One of the major advantages of using a related donor is the possibility of collecting or generating additional cellular products from the same donor to open the possibility of enhancing both the antitumor effects of the graft and the immunologic reconstitution after transplantation.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"05 1","pages":"115 - 119"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1572322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58126847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metaiodobenzylguanidine and Neuroblastoma 偏十二苄基胍与神经母细胞瘤

Journal of pediatric biochemistry Pub Date : 2015-12-01 DOI: 10.1055/s-0036-1572362

J. Balaguer, J. L. Loaiza, A. Di Cataldo, P. Bello, A. Cañete, V. Castel

引用次数: 0

Molecular Pathways in Childhood Acute Lymphoblastic Leukemia: From the Bench to the Bedside 儿童急性淋巴细胞白血病的分子途径:从实验室到床边

Journal of pediatric biochemistry Pub Date : 2015-12-01 DOI: 10.1055/s-0036-1572421

P. Bonaccorso, Nellina Andriano, V. Iachelli, Manuela La Rosa, P. Samperi, Emanuela Cannata, L. Lo Valvo, M. La Spina, A. Di Cataldo, G. Russo, L. Lo Nigro

{"title":"Molecular Pathways in Childhood Acute Lymphoblastic Leukemia: From the Bench to the Bedside","authors":"P. Bonaccorso, Nellina Andriano, V. Iachelli, Manuela La Rosa, P. Samperi, Emanuela Cannata, L. Lo Valvo, M. La Spina, A. Di Cataldo, G. Russo, L. Lo Nigro","doi":"10.1055/s-0036-1572421","DOIUrl":"https://doi.org/10.1055/s-0036-1572421","url":null,"abstract":"Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, originating from a neoplastic deviation of B or T lymphocyte. Cytogenetic, cytofluorimetric, and genomic analyses clearly defined several subtypes of ALL. However, the leukemogenic process is characterized by different pathways' alteration which are still to be determined, in the attempt to identify specific targets to be druggable. In this review, we explore the main molecular pathways, which are commonly shared between different subtypes of pediatric ALL. These cell-signaling pathways affect many functions, including cell proliferation, apoptosis, migration, and differentiation. The PI3K/AKT/mTOR pathway is one of the most studied, with higher expected promises of being targetable. RAS pathway is also widely studied in all types of cancer. The Wnt/Beta catenin has been recently studied in ALL. Finally, CXCL12/CXCL4 axis has a crucial role in regulating hematopoietic stem cell and bone marrow niche. The complete characterization of these pathways will allow us to design a specific patient–disease profile associated with a tailored treatment, with the highest grade of efficacy and the lowest grade of toxicity.","PeriodicalId":89425,"journal":{"name":"Journal of pediatric biochemistry","volume":"05 1","pages":"146 - 156"},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1055/s-0036-1572421","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58127131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Bone Sarcomas in Children and Adolescents 儿童和青少年的骨肉瘤

Journal of pediatric biochemistry Pub Date : 2015-12-01 DOI: 10.1055/s-0036-1572424

P. D’Angelo, F. Di Marco, F. Ferraro, C. Mosa, Angela Trizzino, Serena Tropia

引用次数: 0