RESUMO

A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.

Assuntos

Fertilização in vitro , Folículo Ovariano , Indução da Ovulação , Taxa de Gravidez , Humanos , Feminino , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/patologia , Gravidez , Indução da Ovulação/métodos , Fertilização in vitro/métodos , Nascido Vivo/epidemiologia , Insuficiência Ovariana Primária/patologia , Hormônio Foliculoestimulante

RESUMO

Mucopolysaccharidosis (MPS) IVA is a lysosomal storage disorder caused by mutations in the GALNS gene that leads to the lysosomal accumulation of keratan sulfate (KS) and chondroitin 6-sulfate, causing skeletal dysplasia and cardiopulmonary complications. Current enzyme replacement therapy does not impact the bone manifestation of the disease, supporting that new therapeutic alternatives are required. We previously demonstrated the suitability of the CRISPR-nCas9 system to rescue the phenotype of human MPS IVA fibroblasts using iron oxide nanoparticles (IONPs) as non-viral vectors. Here, we have extended this strategy to an MPS IVA mouse model by inserting the human GALNS cDNA into the ROSA26 locus. The results showed increased GALNS activity, mono-KS reduction, partial recovery of the bone pathology, and non-IONPs-related toxicity or antibody-mediated immune response activation. This study provides, for the first time, in vivo evidence of the potential of a CRISPR-nCas9-based gene therapy strategy for treating MPS IVA using non-viral vectors as carriers.

RESUMO

Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children's Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings. Methods: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases. Results: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (n = 10, 41.66%) and p.(Arg386Cys) (n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]. Conclusion: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.

RESUMO

Preventing the replication of adenovirus could have practical uses, such as controlling infection with wild-type virus or in applications involving recombinant vectors. Mainly transient methods have been used to inhibit adenovirus replication, including siRNA or drugs. Here, we tested whether stable expression of shRNA designed to target hexon, Iva2, or pol can inhibit the replication of a recombinant adenoviral vector, Ad-LacZ (serotype 5, E1/E3 deleted), in 293T cells. Significant knockdown correlating with reduced Ad-LacZ replication was achieved only when hexon was targeted. Cell sorting and isolation of cellular clones further accentuated knockdown of the hexon transcript, reduced protein levels by more than 90%, and diminished adenovirus production. As visualized by transmission electron microscopy, the cellular clone expressing the hexon-specific shRNA yielded 89.2% fewer particles compared to the parental 293T cells. Full scale production followed by purification revealed a 90.2% reduction in Ad-LacZ biological titer. These results support the notion that stable expression of shRNA can be used as a means to control adenovirus replication.

RESUMO

Colombia has a high prevalence of mucopolysaccharidosis (MPS) type IVA. Nevertheless, data regarding the mutation spectrum for MPS IVA in this population have not been completely characterized. Forty-seven families and 53 patients from seven different Colombian regions were tested for MPS IVA mutations. We compared the sequences with the N-acetylgalactosamine-6-sulfatase (GALNS) reference sequence NM_000512.4, and gene variants were reported. Bioinformatics analysis was performed using SWISS-MODEL. The mutant proteins were generated by homology from the wild-type GALNS 4FDJ template obtained from the PDB database, and visualization was performed using Swiss-PDBViewer and UCSF Chimera. The predictive analysis was run using different bioinformatic tools, and the deleterious annotation of genetic variants was performed using a neural network. We found that 79% and 21% of the cohort was homozygous and compound heterozygous, respectively. The most frequent mutation observed was p.Gly301Cys (78.3% of alleles), followed by p.Arg386Cys (10.4% of alleles). A novel mutation (p.Phe72Ile) was described and classified in silico as a pathogenic variant. This study reveals the mutation spectrum of MPS IVA in Colombia. The high prevalence of the p.Gly301Cys mutation suggests a founder effect of this variant in the Colombian population that causes diseases in the Andean region (via migration). These data can facilitate genetic counseling, prenatal diagnosis, and the design of therapeutic interventions.

Assuntos

Condroitina Sulfatases , Mucopolissacaridose IV , Alelos , Condroitina Sulfatases/genética , Colômbia/epidemiologia , Feminino , Humanos , Mucopolissacaridose IV/epidemiologia , Mucopolissacaridose IV/genética , Mutação , Gravidez

RESUMO

BACKGROUND: There is a paucity of real-world epidemiological data on patients with mucopolysaccharidoses (MPS) in Latin America. This real-world study assessed the disease burden, management patterns and multidisciplinary clinical approaches for MPS-IVA and MPS-VI patients in Latin America (Colombia, Ecuador, Mexico, Peru). METHODS: Data were collected from physicians/specialists experienced in treating MPS patients between April-June 2020, via an online patient-diary survey. RESULTS: Overall, 29 physicians/specialists participated in this study. Data from 98 patients were analyzed (MPS-IVA, 71 patients and MPS-VI, 27 patients). Mean age for MPS-IVA patients was 17.5 years and for MPS-VI patients was 11.6 years, and the majority were females (52% and 78%, respectively). MPS-IVA and VI patients presented a high absenteeism from school (55% and 37%, respectively; <18 years age) and workplace (78% and 100%, respectively; >18 years age), indicating an impact of the disease on some aspects of the patients' quality of life. The onset of the first symptom occurred at the age of 3.1 years for MPS-IVA patients and at 1 year for MPS-VI, with delay in diagnosis (3.5-3.9 years from symptom onset) and enzyme replacement therapy (ERT) initiation (1.1-3.6 years from diagnosis). ERT interruptions were observed for MPS-IVA (48%) and MPS-VI patients (44%), with non-availability of medication recorded as the main reason for non-adherence (46% and 60% patients, respectively). ERT showed noticeable treatment benefits in MPS-IVA/VI patients, with stabilization/reduction in complications or the number of surgeries. A multidisciplinary clinical team approach was used for patient management. CONCLUSION: The disease burden for MPS-IVA/VI was high in Latin America, with consistent management, treatment and socio-demographic trends throughout the region.

RESUMO

Resumen: Las dilataciones biliares son malformaciones congénitas raras que pueden involucrar la totalidad de la vía biliar, más comunes durante la primera década de la vida. La mayoría de los casos se presentan con dolor abdominal crónico localizado en cuadrante superior derecho e ictericia. La alta sospecha clínica acompañada de estudios de imagen son indispensables para el diagnóstico. El tratamiento ha evolucionado hasta que en la actualidad la resección completa de los quistes se ha convertido en el manejo de elección, ya que presenta buena respuesta, aunque sin quedar exentos de complicaciones a largo plazo. Presentamos el caso de un paciente del sexo masculino, de 27 años de edad, con historia de dolor abdominal epigástrico de 3 meses de evolución, diagnosticado como quiste de colédoco Todani IVa por resonancia magnética. Se realizó manejo quirúrgico abierto con resección total del quiste y derivación biliodigestiva en Y de Roux sin complicaciones. Fue egresado a los 7 días postoperatorios sin eventualidades. Se realizó revisión de la literatura enfocada en el abordaje y manejo quirúrgico de casos similares.

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Abstract: Biliary tree dilations are unusual congenital malformations that may involve the entire bile circulation and they are common during the first life decade. Most cases initiate with jaundice and chronic abdominal pain which localizes in right upper quadrant. High clinical suspicion accompanied by imaging studies are essential for diagnosis. Treatment has evolved until today complete cyst resection has become the treatment of choice, since it presents a good response, although without being free from long-term complications. We present the case of a 27-year-old male patient with a history of 3 months onset epigastric abdominal pain diagnosed as Todani IVa common bile duct choledochal cyst by magnetic resonance imaging. Open surgical management was performed with total resection of the cyst and biliodigestive Roux-en-Y diversion without any complications. He was discharged 7 days post-op. A review of the literature focused on the surgical approach and management of similar cases was carried out.

RESUMO

Mucopolysaccharidosis type IVA (MPS IVA) is a lysosomal storage disease produced by the deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme, leading to glycosaminoglycans (GAGs) accumulation. Since currently available treatments remain limited and unspecific, novel therapeutic approaches are essential for the disease treatment. In an attempt to reduce treatment limitations, gene therapy rises as a more effective and specific alternative. We present in this study the delivery assessment of GALNS and sulfatase-modifying factor 1 (SUMF1) genes via HIV-1 derived lentiviral vectors into fibroblasts from MPS IVA patients. After transduction, we determined GALNS enzymatic activity, lysosomal mass change, and autophagy pathway impairment. Additionally, we computationally assessed the effect of mutations over the enzyme-substrate interaction and phenotypic effects. The results showed that the co-transduction of MPS IVA fibroblasts with GALNS and SUMF1 cDNAs led to a significant increase in GALNS enzyme activity and a reduction of lysosomal mass. We show that patient-specific differences in cellular response are directly associated with the set of mutations on each patient. Lastly, we present new evidence supporting autophagy impairment in MPS IVA due to the presence and changes in autophagy proteins in treated MPS IVA fibroblasts. Our results offer new evidence that demonstrate the potential of lentiviral vectors as a strategy to correct GALNS deficiency.

Assuntos

Condroitina Sulfatases , Fibroblastos/metabolismo , Vetores Genéticos , HIV-1 , Mucopolissacaridose IV , Oxirredutases atuantes sobre Doadores de Grupo Enxofre , Transdução Genética , Condroitina Sulfatases/biossíntese , Condroitina Sulfatases/genética , Terapia Genética , Células HEK293 , Humanos , Mucopolissacaridose IV/genética , Mucopolissacaridose IV/metabolismo , Mucopolissacaridose IV/terapia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/biossíntese , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética

RESUMO

Complex recombinant glycoproteins produced as potential biopharmaceuticals in goat's milk have an aberrant pattern of N-glycosylation due to the lack of multi-antennary structures. Overexpression of glycosyltransferases may increase oligosaccharide branching of the desired glycoproteins. Here, human erythropoietin fused to human IgG Fc (EPO-Fc) was co-expressed with N-acetyl-glucosaminyltransferase-IVa (GnT-IVa) by adenoviral transduction in goat mammary gland to evaluate the in vivo modification of N-glycosylation pattern in this tissue. Adenoviral vectors, containing the EPO-Fc and GnT-IVa sequences were assembled for in vitro and in vivo expression in mammalian cell culture or in goat mammary gland. Protein detection was assessed by gel electrophoresis and western blot, and N-glycans were identified by HPLC and mass spectrometry. GnT-IVa overexpression and its colocalization with EPO-Fc in the Golgi apparatus of SiHa cells were demonstrated. N-glycan analysis of in vitro and in vivo expression of EPO-Fc modified by GnT-IVa (EPO-Fc/GnT-IVa) showed an increase in high molecular weight structures, which corresponded to tri- and tetra-antennary N-glycans in SiHa cells and mostly tri-antennary N-glycans in goat's milk from transformed mammary tissue. The results confirmed that successful modification of the goat mammary gland secretion pathway could be achieved by co-expressing glycoenzymes together with the glycoprotein of interest. This is the first report of modification of the N-glycosylation pattern in the goat mammary gland in vivo, and constitutes a step forward for improving the use of the mammary gland as a bioreactor for the production of complex recombinant proteins.

Assuntos

Glicoproteínas/metabolismo , Glândulas Mamárias Animais/metabolismo , Animais , Células Cultivadas , Eritropoetina , Feminino , Glicosilação , Cabras , Humanos , N-Acetilglucosaminiltransferases , Transdução Genética

RESUMO

Electrostatic interactions between phosphate anions and Toll-like receptor 4 / Myeloid differentiation factor-2 (TLR4/MD-2) protein complexes of human, murine, equine and canine species were computed. Such knowledge can provide mechanistic information about recognising LPS-like ligands, since anionic phosphate groups belong to the structural features of LPS with their diphosphorylated diglucosamine backbone. Sequence composition analyses, electrostatic interaction potentials and docked energies as well as molecular dynamics studies evaluated the phosphate interactions within the triangular LPS binding site (wedge). According to electrostatic analyses, human, horse and dog wedges possess phosphate-binding sites with indistinct positive and negative charge distributions, but the murine wedge shows a unique strong negative net charge at the site where antagonists bind in other species (Pan). Docking of a phosphate mono-anion (probe) confirmed its repulsion at this Pan site, but the Pag site of the murine wedge attracted the probe. It is occupied by phosphate groups of agonists in other species (Pag). Molecular dynamics trajectories show a variable degree of random walk across the wedges, that is, not following electrostatic preferences (neither Pag nor Pan). In summary, two opposing electrostatic patterns exist -murine versus human, equine and canine species - all of which reflect the potential dual activity mode of under-acylated ligands such as lipid IVA.

Assuntos

Lipídeos/química , Fosfatos/química , Receptor 4 Toll-Like/química , Sequência de Aminoácidos , Animais , Cães , Cavalos , Humanos , Imunidade Inata , Camundongos , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Eletricidade Estática , Relação Estrutura-Atividade

RESUMO

Abstract The safety and efficacy of elosulfase alfa were evaluated in a multicenter, open-label, phase 3b study in Australian Morquio A patients, consisting of a 49-week initial phase and an extension phase until elosulfase alfa was government funded. Thirteen patients (1-27 years) were enrolled. No new safety concerns were identified over 138 weeks. Most drug-related adverse events were mild or moderate in severity; none led to study discontinuation. After 49 weeks of treatment, median improvements from baseline were seen in the 6-minute walk test (+41.0 m), 3-minute stair climb test (+14.0 stairs/min), forced vital capacity (+16.4%), forced expiratory volume in 1 second (+14.1%), urine keratan sulfate (-7.1 µg/mg creatinine), and pain intensity. Growth, cardiac function, sleep, and quality of life results were mixed or stable. These results provide further evidence of the acceptable safety/tolerability profile of elosulfase alfa. The improvements in endurance, pulmonary function, and pain support findings from previous studies.

RESUMO

A study published in 2012 estimated incidence of MPS IVA, in 0.68 cases per 100, 000 live births in Colombia, and according to the Colombian Fund for High-Cost Diseases, in 2014 there were 15 people diagnosed with MPS IV. To enhance the knowledge of the disease in the country, we aimed to characterize clinical and molecular findings in 12 MPS IVA patients. Twelve patients were included in the study, with most patients of female gender (n = 7, 58,3%), age range 2 to 28 years, average weight 26 kg (17.6-43 kg), average height 97 cm (92-104 cm), average BMI 27.6 kg/m2 (19.92-47.65 kg/m2). Clinical findings were similar to those described in the literature. GALNS gene molecular analysis showed five homozygous missense mutations in exon 11 c.1156C > T or p.R386C, a single nonsense mutation in the heterozygous state c.974G > A p.W325, and heterozygous in exon 9 mutation of exon 3 c.280C > T p.R94C, missense variant reported by Ogawa in 1995 [17]. There was only one patient that presented a homozygous missense mutation in exon 9 c.901G > T p.G301C and four patients showed the heterozygous form. A heterozygous missense mutation in exon 5 c.425A > T p.H142L, which has not been previously reported, was found in a female patient, 2 years 11 months of age. The diagnosis algorithms that include molecular analysis, bioinformatic predictive tools, pharmacogenomics, and proteomics helps to improve the diagnosis, treatment, and prognosis of patients affected by MPS IVA.

RESUMO

BACKGROUND: As mucopolysaccharidosis IVA (MPS IVA) is the most frequent MPS in Colombia, this paper aims to describe its clinical and mutational characteristics in 32 diagnosed patients included in this study. METHODS: Genotyping was completed by amplification and Sanger sequencing of the GALNS gene. The SWISS-model platform was used for bioinformatic analysis, and mutant proteins were generated by homology from the wild-type GALNS code 4FDI template from the Protein Data Bank (PDB) database. Docking was performed using the GalNAc6S ligand (PubChem CID: 193456) by AutoDock Vina 1.0 and visualized in PyMOL and LigPlot+. RESULTS: Eleven variants were identified, and one new pathogenic variant was described in the heterozygous state, which is consistent with genotype c. 319 G> T or p.Ala107Ser. The pathogenic variant c.901G>T or p.Gly301Cys was the most frequent mutation with 51.6% of alleles. Docking revealed affinity energy of -5.9 Kcal/mol between wild-type GALNS and the G6S ligand. Some changes were evidenced at the intermolecular interaction level, and affinity energy for each mutant decreased. CONCLUSION: Clinical variables and genotypic analysis were similar to those reported for other world populations. Genotypic data showed greater allelic heterogeneity than those previously reported. Bioinformatics tools showed differences in the binding interactions of mutant proteins with the G6S ligand, in regard the wild-type GALNS.

RESUMO

BACKGROUND: Multimodal strategy including chemotherapy and hepatectomy is advocated for the management of colorectal liver metastases (CRLM). The aim of this study was to evaluate the impact of neoadjuvant Bevacizumab-based chemotherapy on survival in patients with resected stage IVA colorectal cancer and liver metastases. METHODS: Data from 120 consecutive patients who received neoadjuvant chemotherapy and underwent curative-intent hepatectomy for synchronous CRLM were retrospectively reviewed. Overall survival (OS) was stratified according to administration of Bevacizumab before liver resection and surgical strategy, i.e., classical strategy (primary tumor resection first) versus reverse strategy (liver metastases resection first). RESULTS: Patients who received Bevacizumab (n = 37; 30%) had a higher number of CRLM (p = 0.003) and underwent more often reverse strategy (p = 0.005), as compared to those who did not (n = 83; 70%). Bevacizumab was associated with an improved OS compared with conventional chemotherapy (p = 0.04). After stratifying by the surgical strategy, Bevacizumab was associated with improved OS in patients who had classical strategy (p = 0.03). In contrast, Bevacizumab had no impact on OS among patients who had liver metastases resection first (p = 0.89). CONCLUSIONS: Neoadjuvant Bevacizumab-based chemotherapy was associated with improved OS in patients who underwent liver resection of synchronous CRLM, especially in those who underwent primary tumor resection first.

Assuntos

Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Terapia Neoadjuvante/métodos , Adulto , Idoso , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/mortalidade , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/mortalidade , Estudos Retrospectivos , Resultado do Tratamento

RESUMO

The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine the role of cPLA2α in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). WT C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice [WT-bone marrow transplant (BMT)] or mice deficient in cPLA2α (KO-BMT). After full engraftment, mice underwent UUO and kidneys were collected 3, 7, and 14 days after injury. Using picrosirius red, collagen-3, and smooth muscle α actin staining, we determined that renal fibrosis was significantly attenuated in KO-BMT animals as compared with WT-BMT animals. Lipidomic analysis of homogenized kidneys demonstrated a time-dependent upregulation of pro-inflammatory eicosanoids after UUO; KO-BMT animals had lower levels of many of these eicosanoids. KO-BMT animals also had fewer infiltrating pro-inflammatory CD45+CD11b+Ly6Chi macrophages and reduced message levels of pro-inflammatory cytokines. Our results indicate that cPLA2α and/or its downstream mediators, produced by bone marrow-derived cells, play a major role in eicosanoid production after renal injury and in renal fibrinogenesis.

Assuntos

Medula Óssea/metabolismo , Fosfolipases A2 do Grupo IV/metabolismo , Nefropatias/metabolismo , Obstrução Ureteral/metabolismo , Animais , Fibrose/metabolismo , Fibrose/patologia , Fosfolipases A2 do Grupo IV/deficiência , Fosfolipases A2 do Grupo IV/genética , Nefropatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Obstrução Ureteral/patologia

RESUMO

El Síndrome de Morquio es un trastorno de almacenamiento de mucopolisacáridos se caracteriza principalmente por estatura corta y afectación ósea grave, pero el coeficiente intelectual es normal. La prevalencia es rara se estima que afecta a uno de cada 200.000 nacimientos hombres y mujeres por igual. La MPS IV A y B son enfermedades autosómicas recesivas con esto queremos decir que ambos progenitores son portadores del mismo gen afectado el cual se encuentra alterado produciendo así una deficiencia en la producción de la enzima. Las manifestaciones esqueléticas en esta displasia son retardo en el crecimiento, hipoplasia del odontoides, cifosis toracolumbar, displasia de cadera, genu valgo, manchas cutáneas y laxitud articular, en cuando a cuestiones dentales tenemos: el esmalte es delgado, rugoso e hipoplásico afectando dientes deciduos como permanentes. Se presenta el caso de un paciente masculino de 8 años 3/12 presentando MPS el cual requiere un protocolo de rehabilitación lo cual se realiza en el área de odontopedriatría del Hospital del Niño DIF.

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Morquio syndrome is a mucopolysaccharide storage disorder is mainly characterized by short stature, severe bone involvement, but IQ is normal. The prevalence is rare is estimated to affect one in every 200,000 births men and women alike. The MPS IV A and B are autosomal recessive diseases with this we mean that both parents are carriers of the same gene affected which is altered thus producing a deficiency in the production of the enzyme. The skeletal manifestations in this dysplasia are growth retardation, hypoplasia of the odontoid, thoracolumbar kyphosis, hip dysplasia, genu valgus, skin blemishes and joint laxity, then dental issues are: the enamel is thin rugged and hypoplastic affecting deciduous theeth as permanent. The case of a male patient presenting eight years 3/12 MPS which requires a rehabilitation protocol which is done in the dental area of Hospital del Niño DIF is presented.

Assuntos

Humanos , Masculino , Criança , Doenças Dentárias/terapia , Mucopolissacaridose IV/complicações , Doenças Dentárias/congênito , Doenças Dentárias/diagnóstico por imagem , Radiografia Panorâmica , Mucopolissacaridose IV/diagnóstico , Mucopolissacaridose IV/terapia

RESUMO

Morquio A disease (Mucopolysaccharidosis type IVA, MPS IVA) is one of the 11 mucopolysaccharidoses (MPSs), a heterogeneous group of inherited lysosomal storage disorders (LSDs) caused by deficiency in enzymes need to degrade glycosaminoglycans (GAGs). Morquio A is characterized by a decrease in N-acetylgalactosamine-6-sulfatase activity and subsequent accumulation of keratan sulfate and chondroitin 6-sulfate in cells and body fluids. As the pathophysiology of this LSD is not completely understood and considering the previous results of our group concerning oxidative stress in Morquio A patients receiving enzyme replacement therapy (ERT), the aim of this study was to investigate oxidative stress parameters in Morquio A patients at diagnosis. It was studied 15 untreated Morquio A patients, compared with healthy individuals. The affected individuals presented higher lipid peroxidation, assessed by urinary 15-F2t-isoprostane levels and no protein damage, determined by sulfhydryl groups in plasma and di-tyrosine levels in urine. Furthermore, Morquio A patients showed DNA oxidative damage in both pyrimidines and purines bases, being the DNA damage positively correlated with lipid peroxidation. In relation to antioxidant defenses, affected patients presented higher levels of reduced glutathione (GSH) and increased activity of glutathione peroxidase (GPx), while superoxide dismutase (SOD) and glutathione reductase (GR) activities were similar to controls. Our findings indicate that Morquio A patients present at diagnosis redox imbalance and oxidative damage to lipids and DNA, reinforcing the idea about the importance of antioxidant therapy as adjuvant to ERT, in this disorder.

RESUMO

The aim of this research was to evaluate the feasibility of rescuing adult plants by cuttings from post-fire epicormic shoots. We evaluated the native tree species erva mate ( Ilex paraguariensis St. Hil.) and canjerana ( Cabralea canjerana Vell. Mart.), which present difficult seedling production and are economically and ecologically important. The plant material used for the preparation of cuttings consisted of shoots from bud differentiation of tissue from the stem collar of the trees. One-bud cuttings of erva mate were treated with 4000 or 8000mg L-1 of indolebutiric acid (IBA) and the checks were not treated with auxins. The cuttings were grown in three different substrates: carbonized rice husks, vermiculite and coarse sand. The experiment was a factorial with a completely random design and five replicates of five cuttings. One-bud cuttings from the basal, intermediate and apical parts of canjerna shoots were treated with 0 or 6000mg L-1 of IBA and planted in commercial substrate and coarse sand (3:2 v/v). The experiment was a factorial with a completely random design and ten replicates of three cuttings. Cuttings from post-fire epicormic shoots can be used for rescuing erva mate and canjerana adult plants. Erva mate cuttings treated with 8000mgL-1 IBA have increased rooting when grown in coarse sand. Canjerana cuttings from the basal part of epicormic shoots have greater survival and rooting than those from intermediate and apical parts.

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O objetivo deste trabalho foi avaliar a possibilidade de resgatar árvores adultas por estaquia de brotos epicórmicos de rebrota pós-fogo. Foram estudadas a erva-mate ( Ilex paraguariensis St. Hil.) e a canjerana ( Cabralea canjerana Vell. Mart.), que são espécies nativas de difícil propagação por sementes e de relevante importância econômica e ecológica. O material vegetativo utilizado para o preparo das estacas foi constituído de brotos, provenientes da rebrota da diferenciação dos tecidos de gemas do colo de árvores matrizes com, aproximadamente, 20 anos de idade. Para a erva-mate, estacas de gema única foram tratadas com 4000 e 8000mg L-1 de ácido indolbutírico (IBA), e as testemunhas que não receberam tratamento auxínico. As estacas foram cultivadas em três diferentes substratos: casca de arroz carbonizada, vermiculita e areia de granulometria grossa. O experimento foi um fatorial no delineamento inteiramente casualizado, com cinco repetições de cinco estacas. Para canjerana, estacas basais, medianas e apicais de gema única, foram ou não tratadas com 6000mg L-1 de IBA e cultivadas em substrato comercial e areia de granulometria grossa (3:2 v/v). O experimento foi um fatorial no delineamento inteiramente casualizado, com dez repetições de três estacas. A estaquia de rebrota pós-fogo pode ser utilizada para o resgate de árvores adultas de erva-mate e canjerana. Estacas de erva-mate tratadas com 8000mg L-1 de IBA enraízam melhor em areia grossa. Estacas de canjerana, obtidas da porção basal das brotações, apresentam maior sobrevivência e enraizamento do que as medianas e apicais.

Assuntos

Ilex paraguariensis , Incêndios , Árvores , Brotos de Planta , Reguladores de Crescimento de Plantas

RESUMO

The aim of this research was to evaluate the feasibility of rescuing adult plants by cuttings from post-fire epicormic shoots. We evaluated the native tree species erva mate ( Ilex paraguariensis St. Hil.) and canjerana ( Cabralea canjerana Vell. Mart.), which present difficult seedling production and are economically and ecologically important. The plant material used for the preparation of cuttings consisted of shoots from bud differentiation of tissue from the stem collar of the trees. One-bud cuttings of erva mate were treated with 4000 or 8000mg L-1 of indolebutiric acid (IBA) and the checks were not treated with auxins. The cuttings were grown in three different substrates: carbonized rice husks, vermiculite and coarse sand. The experiment was a factorial with a completely random design and five replicates of five cuttings. One-bud cuttings from the basal, intermediate and apical parts of canjerna shoots were treated with 0 or 6000mg L-1 of IBA and planted in commercial substrate and coarse sand (3:2 v/v). The experiment was a factorial with a completely random design and ten replicates of three cuttings. Cuttings from post-fire epicormic shoots can be used for rescuing erva mate and canjerana adult plants. Erva mate cuttings treated with 8000mgL-1 IBA have increased rooting when grown in coarse sand. Canjerana cuttings from the basal part of epicormic shoots have greater survival and rooting than those from intermediate and apical parts. (AU)

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O objetivo deste trabalho foi avaliar a possibilidade de resgatar árvores adultas por estaquia de brotos epicórmicos de rebrota pós-fogo. Foram estudadas a erva-mate ( Ilex paraguariensis St. Hil.) e a canjerana ( Cabralea canjerana Vell. Mart.), que são espécies nativas de difícil propagação por sementes e de relevante importância econômica e ecológica. O material vegetativo utilizado para o preparo das estacas foi constituído de brotos, provenientes da rebrota da diferenciação dos tecidos de gemas do colo de árvores matrizes com, aproximadamente, 20 anos de idade. Para a erva-mate, estacas de gema única foram tratadas com 4000 e 8000mg L-1 de ácido indolbutírico (IBA), e as testemunhas que não receberam tratamento auxínico. As estacas foram cultivadas em três diferentes substratos: casca de arroz carbonizada, vermiculita e areia de granulometria grossa. O experimento foi um fatorial no delineamento inteiramente casualizado, com cinco repetições de cinco estacas. Para canjerana, estacas basais, medianas e apicais de gema única, foram ou não tratadas com 6000mg L-1 de IBA e cultivadas em substrato comercial e areia de granulometria grossa (3:2 v/v). O experimento foi um fatorial no delineamento inteiramente casualizado, com dez repetições de três estacas. A estaquia de rebrota pós-fogo pode ser utilizada para o resgate de árvores adultas de erva-mate e canjerana. Estacas de erva-mate tratadas com 8000mg L-1 de IBA enraízam melhor em areia grossa. Estacas de canjerana, obtidas da porção basal das brotações, apresentam maior sobrevivência e enraizamento do que as medianas e apicais. (AU)

Assuntos

Árvores , Ilex paraguariensis , Incêndios , Brotos de Planta , Reguladores de Crescimento de Plantas

RESUMO

Abstract Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by a deficient N-acetylgalactosamine-6-sulfate sulfatase activity, leading to cellular storage of undegraded keratan sulfate. Recently enzyme replacement therapy (ERT) was approved for MPS IVA, but some of ERT effects are still unknown. In the present study, we aimed to evaluate the efficacy of elosulfase alfa upon glycosaminoglycan (GAG) storage in peripheral blood white blood cells of patients with MPS IVA treated for 6 months, comparing samples from patients who received weekly infusions of enzyme (ERT-W) versus infusions every other week (ERT-EOW) versus placebo. A significant reduction in GAG storage was observed in both ERT-treated groups, with weekly ERT showing slightly better performance than ERT-EOW.