RESUMO
INTRODUCTION: Vitamin D acts on the immune system and lung response. Patients with cystic fibrosis (CF) may be deficient in this vitamin. The aims of the study were to evaluate vitamin D levels and severity of lung disease in infants and preschoolers diagnosed with CF, and to compare them to a group of children without pancreatic insufficiency (PI). METHODS: Patients with CF up to 4 years old were included, and compared to an age-matched group of children without diagnosis of CF. CF group had medical records and High Resolution Thorax Computed Tomography (HRCCT) evaluated in order to verify the severity of lung disease. Information on demographic data, sun exposure habits, supplemental vitamin D therapy, and on the season at the time of vitamin D sampling were collected for both groups. RESULTS: This study included 45 patients in the CF group and 102 in the non-CF group, with no differences in age (P = 0.327) between them. There was no association between vitamin D levels and markers of lung disease in the CF group. The non-CF group had lower daily sun exposure (P = 0.034), and lower supplementation than the CF group (P < 0.001). Supplementation and seasonality were the determinant variables for vitamin D levels, which were lower for non-supplemented children and for assessments during fall/winter. CONCLUSION: There was no association between lung disease severity and vitamin D levels in CF group. Supplementation and seasonality were associated to higher vitamin levels.
Assuntos
Fibrose Cística/epidemiologia , Insuficiência Pancreática Exócrina/epidemiologia , Estações do Ano , Luz Solar , Deficiência de Vitamina D/epidemiologia , Biomarcadores , Pré-Escolar , Fibrose Cística/diagnóstico por imagem , Fibrose Cística/metabolismo , Insuficiência Pancreática Exócrina/metabolismo , Feminino , Humanos , Lactente , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Tomografia Computadorizada por Raios X , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/metabolismoRESUMO
A insuficiência pancreática exócrina é uma incapacidade na secreção de enzimas digestivas decorrentes da diminuição do tecido acinar do pâncreas acarretando uma má digestão e absorção. O presente trabalho relata o caso de uma cadela SRD de um ano e meio com histórico de emagrecimento, esteatorréia, burburinhos e polifagia que foi diagnostica com insuficiência pancreática exócrina após teste de imunorreatividade da tripsina. O tratamento instituído com suplementação de enzimas pancreáticas foi eficiente no controle e evolução da doença.(AU)
Exocrine pancreatic insufficiency is the inability to secrete digestive enzymes due to the decrease in the acinar tissue of the pancreas leading to poor digestion and absorption. This work is a case report of a 1.5-years' old mongrel bitch with a history of weight loss, steatorrhea, rumbling sounds and polyphagia that was diagnosed with exocrine pancreatic insufficiency after a trypsin immunoreactivity test. The pancreatic enzyme supplementation was efficient in controlling the evolution of the disease.(AU)
La insuficiencia pancreática exocrina es una incapacidad en la secreción de enzimas digestivas derivadas de la disminución del tejido acinar del páncreas, acarreando mala digestión y absorción. El presente trabajo relata el caso de una perra SRD de un año y medio con historial de adelgazamiento, esteatorrea, burbujas y polifagia que fue diagnosticada con insuficiencia pancreática exocrina después de la prueba de inmune reactividad de la tripsina. El tratamiento instituido con suplementación de enzimas pancreáticas fue eficiente en el control y evolución de la enfermedad.(AU)
Assuntos
Animais , Cães , Insuficiência Pancreática Exócrina/enzimologia , Insuficiência Pancreática Exócrina/metabolismo , Insuficiência Pancreática Exócrina/veterináriaRESUMO
A insuficiência pancreática exócrina é uma incapacidade na secreção de enzimas digestivas decorrentes da diminuição do tecido acinar do pâncreas acarretando uma má digestão e absorção. O presente trabalho relata o caso de uma cadela SRD de um ano e meio com histórico de emagrecimento, esteatorréia, burburinhos e polifagia que foi diagnostica com insuficiência pancreática exócrina após teste de imunorreatividade da tripsina. O tratamento instituído com suplementação de enzimas pancreáticas foi eficiente no controle e evolução da doença.(AU)
Exocrine pancreatic insufficiency is the inability to secrete digestive enzymes due to the decrease in the acinar tissue of the pancreas leading to poor digestion and absorption. This work is a case report of a 1.5-years' old mongrel bitch with a history of weight loss, steatorrhea, rumbling sounds and polyphagia that was diagnosed with exocrine pancreatic insufficiency after a trypsin immunoreactivity test. The pancreatic enzyme supplementation was efficient in controlling the evolution of the disease.(AU)
La insuficiencia pancreática exocrina es una incapacidad en la secreción de enzimas digestivas derivadas de la disminución del tejido acinar del páncreas, acarreando mala digestión y absorción. El presente trabajo relata el caso de una perra SRD de un año y medio con historial de adelgazamiento, esteatorrea, burbujas y polifagia que fue diagnosticada con insuficiencia pancreática exocrina después de la prueba de inmune reactividad de la tripsina. El tratamiento instituido con suplementación de enzimas pancreáticas fue eficiente en el control y evolución de la enfermedad.(AU)
Assuntos
Animais , Cães , Insuficiência Pancreática Exócrina/veterinária , Insuficiência Pancreática Exócrina/enzimologia , Insuficiência Pancreática Exócrina/metabolismoRESUMO
Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined ß-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced ß-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF.
Assuntos
Fibrose Cística/metabolismo , Fibrose Cística/patologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Pâncreas/metabolismo , Pâncreas/patologia , Adolescente , Adulto , Peptídeo C/metabolismo , Insuficiência Pancreática Exócrina/metabolismo , Feminino , Polipeptídeo Inibidor Gástrico/metabolismo , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Incretinas/metabolismo , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Proinsulina/metabolismo , Adulto JovemRESUMO
Ribosome biogenesis in eukaryotes is a complex process that requires the participation of several accessory proteins that are not part of the mature particle. Efl1 is a yeast GTPase required for the cytoplasmic maturation of the 60S ribosomal subunit. Together with Sdo1, the yeast ortholog of the protein mutated in the Shwachman-Diamond Syndrome (SBDS), Efl1 releases the anti-association factor Tif6 from the surface of the 60S subunit allowing the assembly of mature ribosomes. We characterized the structural content and folding stability of the Saccharomyces cerevisiae and human EFL1 GTPases, as well as their enzymatic properties alone and in the presence of Sdo1 and SBDS, respectively. The human and S. cerevisiae EFL1 GTPases are composed of a mixture of α-helices and ß-sheets. Despite being orthologs, the yeast protein elicited a non-two state thermal unfolding behavior while the human EFL1 was highly resistant to thermal denaturation. Steady-state kinetic analyses indicated slow GTP hydrolysis for both EFL1 GTPases, with kcat values of 0.4 and 0.3min(-1) and Km for GTP of 110 and 180µM respectively. In the presence of the effector proteins, their kcat values remained unaltered while the Km decreased twofold suggesting that Sdo1 and SBDS act as nucleotide exchange factors.
Assuntos
Doenças da Medula Óssea/enzimologia , Doenças da Medula Óssea/genética , Insuficiência Pancreática Exócrina/enzimologia , Insuficiência Pancreática Exócrina/genética , GTP Fosfo-Hidrolases/metabolismo , Lipomatose/enzimologia , Lipomatose/genética , Mutação , Proteínas/química , Proteínas/genética , Proteínas Ribossômicas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Doenças da Medula Óssea/metabolismo , Estabilidade Enzimática/genética , Insuficiência Pancreática Exócrina/metabolismo , GTP Fosfo-Hidrolases/química , Humanos , Lipomatose/metabolismo , Desdobramento de Proteína , Proteínas/metabolismo , Proteínas Ribossômicas/química , Proteínas Ribossômicas/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Síndrome de Shwachman-Diamond , TermodinâmicaRESUMO
OBJECTIVE: To characterize the endocrine phenotype of patients with Shwachman-Diamond syndrome (SDS). STUDY DESIGN: Clinically indicated endocrine screening data from 43 patients with SDS or SDS-like presentation were analyzed according to sex, age, and genetic testing. In addition to 25 patients with biallelic Shwachman-Bodian-Diamond syndrome (SBDS) gene mutations, we evaluated 18 patients with cytopenias who were receiving pancreatic enzyme replacement but were without SBDS mutation. We performed a retrospective review of growth records and clinically indicated endocrine evaluations. RESULTS: Of patients with SBDS mutations, 2 had low stimulated growth hormone levels, 2 had mildly elevated thyrotropin levels, 5 had abnormal glucose levels, and 1 had an elevated follicle-stimulating hormone level (post transplantation). In contrast, 1 patient without SBDS mutations had postprandial hyperglycemia and 3 had mildly low free thyroxine levels without short stature. Endocrine abnormalities were identified in 19% of short patients and 26% of the whole group. Of patients with SBDS mutations, 56% had a height expressed in SD units from the mean for age and sex of <-1.8, in contrast to only 12% of patients without SBDS mutations (38% of the whole group). Body mass index z score was significantly greater in the group with SBDS mutations (P<.001). CONCLUSION: Although short stature was more common in patients with SBDS mutations, no consistent endocrine phenotype was observed in patients with SDS regardless of genetic testing.
Assuntos
Doenças da Medula Óssea/genética , Nanismo/genética , Sistema Endócrino/metabolismo , Insuficiência Pancreática Exócrina/genética , Lipomatose/genética , Adolescente , Doenças da Medula Óssea/metabolismo , Criança , Pré-Escolar , Nanismo/metabolismo , Insuficiência Pancreática Exócrina/metabolismo , Feminino , Humanos , Lactente , Lipomatose/metabolismo , Masculino , Mutação , Fenótipo , Estudos Retrospectivos , Síndrome de Shwachman-Diamond , Adulto JovemRESUMO
OBJECTIVE: The objective of the present study is to compare daily weight gain and laboratory analysis (72-hour fecal fat and steatocrit) with fecal elastase-1 (EL-1) when diagnosing pancreatic insufficiency (PI) in infants with cystic fibrosis (CF). METHODS: A total of 39 infants with CF, diagnosed consecutively by newborn screening at 2 referral centers, were included in the study. Daily weight gain and results of laboratory analysis of stool samples were compared using the κ coefficient and the receiver operator characteristic (ROC) curve. RESULTS: Using the criterion of low daily weight gain, the frequency of PI was 92.3%; using the 72-hour fecal fat, steatocrit, and fecal EL-1 tests, the frequency was 42.3%, 86.2%, and 84.6%, respectively. EL-1 was used as the reference test. It was observed that the criteria of low daily weight gain (<50th percentile) and abnormal steatocrit, used together, showed the highest sensitivity (91.3%) and specificity (83.3%) for the diagnosis of PI. CONCLUSIONS: When fecal EL-1 analysis is not immediately available, low daily weight gain associated with abnormal steatocrit can be adopted as a criterion for initiating pancreatic enzyme replacement therapy in infants with CF; however, EL-1 testing should be performed later for confirmation of PI.
Assuntos
Fibrose Cística/diagnóstico , Insuficiência Pancreática Exócrina/diagnóstico , Gorduras/metabolismo , Fezes/química , Crescimento , Elastase Pancreática/metabolismo , Aumento de Peso , Fibrose Cística/complicações , Fibrose Cística/metabolismo , Insuficiência Pancreática Exócrina/etiologia , Insuficiência Pancreática Exócrina/metabolismo , Feminino , Transtornos do Crescimento/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Curva ROC , Valores de Referência , Sensibilidade e EspecificidadeRESUMO
Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF.
Assuntos
Fibrose Cística/metabolismo , Insuficiência Pancreática Exócrina/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Óleos de Plantas/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Fibrose Cística/complicações , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Eritrócitos/química , Insuficiência Pancreática Exócrina/etiologia , Ácidos Graxos Essenciais/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Humanos , Absorção Intestinal , Óleos de Plantas/administração & dosagemRESUMO
Evaluamos el tiempo de desintegración y la actividad digestiva in vitro de ocho suplementos comerciales pancreáticos bajo condiciones de acidez similares a las gastroduodenales. Las muestras se sometieron a un proceso activo de desintegración durante 45 min a pH de 1, 3 o 6, continuándose el proceso a pH en 6, durante 135 min., la actividad de lipasa y tripsina se determinó cada 15 min por titulometría. A pH constante de 6, los productos sin capa entérica y el Creón tuvieron los tiempos de desintegración más cortos; a pH más ácidos, estos tiempos se alargaron, siendo mayores a 90 min en los productos con capa entérica. La actividad de lipasa fue mayor a pH constante de 6 en Creón, Pankreón y Cotazym-C, Onotón y Cotazym-B. Posterior a la exposición a Ph ácido, la biodisponibilidad enzimática disminuyó en todos los productos. El tiempo de desintegración y la activación de las enzimas por ácido deben tomarse en cuenta al prescribir suplementos pancreáticos.