Statement of Argentine pediatric endocrinologists on growth hormone interchangeability

Growth hormone (GH), just like vaccines, antibodies, and other hormones, is a biological medicinal product (BMP); therefore, it is produced by a complex mechanism that is specific to each (trademark) product. BMPs are subjected to prolonged, comprehensive assessment processes and must be approved prior to their use. The patents of early recombinant human GHs are starting to expire, and this has encouraged pharmaceutical companies to manufacture GH in accordance with the processes corresponding to the original products, thus resulting in biosimilar recombinant GH. In Argentina, there are seven different GH trademarks; only one is a biosimilar product: Omnitrope® (Sandoz) is biosimilar to Genotropin® (Pfizer). Other products available in the market include HHT® (Biosidus), Hutrope® (Elly Lilly), NorditropinFlexpro® (Novo Nordisk), Saizen® (Merck), and Zomacton® (Ferring). For an adequate understanding of this article, it is important to outline the characteristics of the different BMPs.1-5Fil: Alonso, Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Balbi, Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Bazán de Casella, María Cristina del Valle. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Belgorosky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Brunetto, Oscar. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Cassinelli, Hamilton Raul. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ciaccio, Marta Graciela Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Keselman, Ana Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Miras, Mirta Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Morín, Analía. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentin

Osteoporosis-pseudoglioma Syndrome: A pediatric case of primary osteoporosis

La osteoporosis es un trastorno para tener en cuenta en niños con patologías crónicas graves o con algunas enfermedades genéticas que predisponen al incremento de la fragilidad ósea. La osteoporosis primaria es una entidad con etiologías emergentes y puede ocurrir en forma sindrómica. La asociación con pliegues retinianos congénitos debe orientar al diagnóstico de osteoporosis-pseudoglioma (OMIM 259770), síndrome poco frecuente (prevalencia de 1/2000000), que se origina por la pérdida de función de la proteína LRP5 (low-density lipoprotein receptor-related protein 5) y compromete la vía de señalización de Wnt/β-catenina. Se presenta el caso de un niño con pliegues retinianos congénitos, ceguera progresiva y múltiples fracturas cuyo estudio clínico, bioquímico y genético confirmó el diagnóstico de osteoporosis primaria debido a una nueva variante inactivante en el gen LRP5 en homocigosis.Osteoporosis should be considered in children with severe chronic diseases or in association with some genetic diseases that bear an increased risk of bone fragility. Primary osteoporosis is an entity in which emerging aetiologies are being recognized. Its association with congenital retinal folds should guide the diagnosis to the Osteoporosis-Pseudoglioma syndrome (OMIM 259770), a rare disease (prevalence of 1/2000000), caused by the loss of function of the protein LRP5 (low-density lipoprotein receptor-related protein 5) resulting in the alteration of the Wnt/β-catenin signalling pathway. We report the case of a child with congenital retinal folds, progressive loss of vision and multiple fractures whose clinical, biochemical and genetic studies confirmed the diagnosis of primary osteoporosis due to a novel homozygous inactivating variant in LRP5.Fil: Braslavsky, Débora. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Scaglia, Paula Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Sanguineti, Nora María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Aza Carmona, Miriam. Universidad Autónoma de Madrid; EspañaFil: Nevado Blanco, Julián. Universidad Autónoma de Madrid; EspañaFil: Lapunzina Badia, Pablo D.. Universidad Autónoma de Madrid; EspañaFil: Fernandez, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Ruiz, Olivia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Carmona, Alejandra. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Szlago, Marina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Arberas, Claudia Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Cassinelli, Hamilton Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Heath, Karen. Universidad Autónoma de Madrid; EspañaFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin

Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome

Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1-/- mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1-/- mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism

Spectropolarimetry of high-redshift obscured and red quasars

Spectropolarimetry is a powerful technique that has provided critical support for the geometric unification model of local active galactic nuclei. In this paper, we present optical (rest-frame UV) Keck spectropolarimetry of five luminous obscured (Type 2) and extremely red quasars (ERQs) at z~2.5. Three objects reach polarization fractions of >10% in the continuum. We propose a model in which dust scattering is the dominant scattering and polarization mechanism in our targets, though electron scattering cannot be completely excluded. Emission lines are polarized at a lower level than is the continuum. This suggests that the emission-line region exists on similar spatial scales as the scattering region. In three objects we detect an intriguing 90 degree swing in the polarization position angle as a function of line-of-sight velocity in the emission lines of Ly-alpha, CIV and NV. We interpret this phenomenon in the framework of a geometric model with an equatorial dusty scattering region in which the material is outflowing at several thousand km/sec. Emission lines may also be scattered by dust or resonantly. This model explains several salient features of observations by scattering on scales of a few tens of pc. Our observations provide a tantalizing view of the inner region geometry and kinematics of high-redshift obscured and extremely red quasars. Our data and modeling lend strong support for toroidal obscuration and powerful outflows on the scales of the UV emission-line region, in addition to the larger scale outflows inferred previously from the optical emission-line kinematics.Comment: 26 pages, MNRAS, in pres

Ocular Manifestations of Juvenile Paget Disease

Objectives: To determine the prevalence and spectrum of retinal changes in juvenile Paget disease

Global consensus recommendations on prevention and management of nutritional rickets

Background: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. Evidence: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. Process: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. Results: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. Conclusion: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required

Structural stability and bioapplicability assessment of hyaluronic acid-chitosan polyelectrolyte multilayers on titanium substrates

10.1002/jbm.a.31854Journal of Biomedical Materials Research - Part A8741061-1074JBMR