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OBJECTIVE: To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. METHODS: 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. RESULTS: GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 µg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. CONCLUSION: GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.
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Asma , Ensaio de Imunoadsorção Enzimática , Transtornos do Crescimento , Hormônio do Crescimento Humano , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I , Índice de Gravidade de Doença , Humanos , Asma/sangue , Masculino , Feminino , Criança , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Transtornos do Crescimento/sangue , Transtornos do Crescimento/etiologia , Hormônio do Crescimento Humano/sangue , Estudos de Casos e Controles , Pré-Escolar , Valores de Referência , Estatísticas não Paramétricas , AdolescenteRESUMO
Abstract Objective To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. Methods 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. Results GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 μg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. Conclusion GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.
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Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.
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BACKGROUND: The utility of insulin-like growth factor type 1 (IGF-1) is well established in the diagnosis of growth hormone deficiency (GHD), whereas IGF-binding protein type 3 (IGFBP-3) has a more controversial role. Most studies evaluated the value of these peptides by assessing their sensitivity and specificity but not considering the low prevalence of GHD among short children (<2%). OBJECTIVE: To evaluate the utility of basal IGF-1 and IGFBP-3 values in the GHD diagnosis process with a Bayesian approach, based on pre- and post-test probability. METHODS: We determined ROC curves, sensitivity, specificity, and positive and negative predictive values for IGF-1 and IGFBP-3 obtained from patients with GHD (n = 48) and GH-sufficient children (n = 175). The data were also analyzed by classifying the children into early childhood and late childhood (girls and boys younger and older than 8 and 9 years, respectively). RESULTS: The area under the curve (AUC) of the receiver operating characteristic curve of IGF-1-SDS (standard deviation score) was greater than that of IGFBP-3-SDS (AUC 0.886 and 0.786, respectively, p = 0.001). In early childhood, the AUC of IGFBP-3-SDS was significantly improved (0.866) and similar to IGF-1-SDS (0.898). IGF-1-SDS, in comparison to IGFBP-3-SDS, had a greater sensitivity (92 vs. 45.8%, respectively), lower specificity (69 vs. 93.8%, respectively), and lower positive predictive value (5.7 vs. 13.1%, respectively), with similar negative predictive values. CONCLUSION: IGF-1-SDS is a useful screening tool in the diagnosis of GHD. Although IGFBP-3-SDS lacks sensitivity, its high specificity supports the role to confirm GHD in short children, especially in early childhood. This strategy could simplify and reduce the necessity of a second laborious and expensive GH stimulation test to confirm the diagnosis of GHD.
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Transtornos do Crescimento/sangue , Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento Humano/deficiência , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Abstract Introduction: Any type of nutritional imbalance experienced during childhood will affect the health of an individual, both in their childhood and their adulthood. Several studies have proved that there is an association between cardiovascular disease (CVD) risk and endocrine and lipid markers at early stages of life. Objective: To establish the relationship between nutritional status (IGF-1 and serum levels of its binding proteins IGFBP-1, IGFBP-2 and IGFBP-3), and CVD risk markers in students aged 7 to 9 years. Materials and methods: Cross-sectional observational study conducted in 84 children attending two schools from Bogotá D.C. and Soacha, Colombia, to identify the relationship between possible variations in CVD risk markers and nutritional status. Sexual development stage, lipid profile, anthropometric data, blood sugar levels and IGF-1 and IGFBP serum levels of all participants were measured. Statistical analysis was conducted using the Pearson's correlation coefficient, the analysis of variance (ANOVA), and the Kruskall-Wallis, Games-Howell and Dunnett's tests. The confidence interval and statistical significance were 95% and p<0.05, respectively. Results: IGFBP-1 and IGFBP-2 levels proportionally decreased as weight increased. An inverse correlation between both proteins and triglyceride levels was found, as well as a direct correlation with HDL cholesterol levels. Conclusions: Alterations in CVD risk markers can be identified during childhood. If said alterations are timely detected, it is possible to adopt preventive and therapeutic actions such as the promotion of public policies aimed at preventing childhood overweight and obesity, which in turn will reduce the risk of developing cardiovascular disease in adulthood.
Resumen Introducción. Los desequilibrios nutricionales en la infancia afectan la salud tanto en la niñez como en la adultez. Estudios previos demuestran la asociación de marcadores endocrinos y lipídicos con riesgo cardiovascular (RCV) desde edades tempranas. Objetivo. Establecer la relación entre estado nutricional (niveles séricos de IGF-1 y sus proteínas enlazantes IGFBP-1, IGFBP-2 e IGFBP-3) y marcadores de RCV en estudiantes de 7 a 9 años. Materiales y métodos. Estudio observacional comparativo transversal realizado en 84 niños de 2 colegios de Bogotá D.C. y Soacha, Colombia, para identificar la relación entre posibles variaciones de marcadores de RCV y estado nutricional. Se midieron los niveles de glucemia y niveles séricos de IGF-1 e IGFBP, el nivel de desarrollo sexual, el perfil lipídico y los valores antropométricos. Para el análisis estadístico se utilizaron el coeficiente de correlación de Pearson, un análisis de varianza (ANOVA) y las pruebas de Kruskal Wallis, Games-Howell y Dunnett. El intervalo de confianza fue del 95% y la significancia estadística, de p<0.05. Resultados. La reducción en los niveles de IGFB-1 e IGFBP-2 fue directamente proporcional al aumento de peso. Por otra parte, se observó una correlación inversa entre ambas proteínas y concentraciones de triglicéridos, y una directa con los niveles colesterol HDL. Conclusiones. Las alteraciones de marcadores de RCV se pueden identificar en la infancia. Si estas son detectadas a tiempo es posible adoptar medidas preventivas y terapéuticas como la promoción de políticas públicas dirigidas prevenir el sobrepeso infantil, lo que a su vez reducirá el riesgo de padecer enfermedades cardiovasculares en edades adultas.
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BACKGROUND & AIMS: Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice. METHODS: Mice with HSC-selective deletion of NRP (ColCre/Nrp1loxP) or synectin (ColCre/synectinloxP) vs. paired Nrp1loxP or synectinloxP mice were fed a control diet or the chronic/binge alcohol feeding model. Several markers of steatosis and inflammation were evaluated. RESULTS: ColCre/Nrp1loxP mice showed less fibrosis, as expected, but also less inflammation and steatosis, with lower hepatic triglyceride content. Similar results were observed in the synectin model. Hepatocytes treated with supernatant of HSCs from ColCre/Nrp1loxP mice compared to supernatant from Nrp1loxP mice were protected against ethanol-induced lipid droplet formation. An adipokine and inflammatory protein array from the supernatant of HSCs with NRP-1 knockdown showed a significant reduction in Igfbp3 (a major insulin-like growth factor-binding protein with multiple metabolic functions) and an increase in SerpinA12 (a serine-protease inhibitor) secretion compared to wild-type HSCs. Recombinant Igfbp3 induced lipid droplets, triglyceride accumulation, and lipogenic genes in hepatocytes in vitro, while SerpinA12 was protective against ethanol-induced steatosis. Finally, Igfbp3 was increased, and SerpinA12 was decreased in serum and liver tissue from patients with alcoholic hepatitis. CONCLUSION: Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling. LAY SUMMARY: Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fígado Gorduroso Alcoólico , Células Estreladas do Fígado/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neuropilina-1/metabolismo , Serpinas/metabolismo , Animais , Modelos Animais de Doenças , Fígado Gorduroso Alcoólico/complicações , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Fibrose/etiologia , Fibrose/imunologia , Inflamação/metabolismo , Camundongos , Inibidores de Serina Proteinase/metabolismo , Transdução de SinaisRESUMO
OBJECTIVE: To examine whether daily zinc and/or multivitamin supplementation reduce biomarkers of environmental enteric dysfunction (EED), systemic inflammation, or markers of growth in a sample of infants from Dar es Salaam, Tanzania. STUDY DESIGN: Subgroup analysis of infants participating in a randomized, double-blind, placebo-controlled trial received daily oral supplementation of zinc, multivitamins, zinc + multivitamins, or placebo for 18 months starting at 6 weeks of age. EED (anti-flagellin and anti-lipopolysaccharide immunoglobulins), systemic inflammation (C-reactive protein and alpha-1-acid glycoprotein), and growth biomarkers (insulin-like growth factor-1 and insulin-like growth factor binding protein-3) were measured via enzyme-linked immunosorbent assay in a subsample of 590 infants at 6 weeks and 6 months of age. EED biomarkers also were measured in 162 infants at 12 months of age. RESULTS: With the exception of anti-lipopolysaccharide IgG concentrations, which were significantly greater in infants who received multivitamins compared with those who did not (1.41 ± 0.61 vs 1.26 ± 0.65, P = .006), and insulin-like growth factor binding protein-3 concentrations, which were significantly lower in children who received zinc compared with those who did not (981.13 ± 297.59 vs 1019.10 ± 333.01, P = .03), at 6 months of age, we did not observe any significant treatment effects of zinc or multivitamins on EED, systemic inflammation, or growth biomarkers. CONCLUSIONS: Neither zinc nor multivitamin supplementation ameliorated markers of EED or systemic inflammation during infancy. Other interventions should be prioritized for future trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00421668.
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Suplementos Nutricionais , Inflamação/sangue , Inflamação/tratamento farmacológico , Enteropatias/sangue , Enteropatias/tratamento farmacológico , Intestino Delgado , Vitaminas/uso terapêutico , Zinco/uso terapêutico , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Humanos , Lactente , Inflamação/complicações , Enteropatias/complicações , Masculino , Tanzânia , Resultado do TratamentoRESUMO
ABSTRACT Purpose To investigate whether intracavernosal injection of short hairpin RNA for IGFBP-3 could improve erectile function in streptozotocin-induced diabetic rats. Materials and methods After 12 weeks of IGFBP-3 short hairpin RNA injection treatment, intracavernous pressure responses to electrical stimulation of cavernous nerves were evaluated. The expression of IGFBP-3 and IGF-1 at mRNA and protein levels were detected by quantitative real-time PCR analysis and Western blot, respectively. The concentration of cavernous cyclic guanosine monophosphate was detected by enzyme-linked immunosorbent assay. Results At 12 weeks after intracavernous administration of IGFBP-3 shRNA, the cavernosal pressure was significantly increased in response to the cavernous nerves stimulation compared to the diabetic group (P<0.05). Cavernous IGFBP-3 expression at both mRNA and protein levels was significantly inhibited. At the same time, cavernous IGF-1 expression was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Cavernous cyclic guanosine monophosphate concentration was significantly increased in the IGFBP-3 shRNA treatment group compared to the diabetic group (P<0.01). Conclusions Gene transfer of IGFBP-3 shRNA could improve erectile function via the restoration of cavernous IGF-1 bioavailability and an increase of cavernous cGMP concentration in the pathogenesis of erectile dysfunction in streptozotocin-induced diabetic rats.
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Animais , Masculino , Pênis/efeitos dos fármacos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/farmacocinética , RNA Interferente Pequeno/farmacocinética , Diabetes Mellitus Experimental/fisiopatologia , Disfunção Erétil/fisiopatologia , Disfunção Erétil/tratamento farmacológico , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Disponibilidade Biológica , Distribuição Aleatória , Western Blotting , Reprodutibilidade dos Testes , Ratos Wistar , Estreptozocina , Diabetes Mellitus Experimental/complicações , Reação em Cadeia da Polimerase em Tempo Real , Disfunção Erétil/etiologia , InjeçõesRESUMO
Introduction Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa). Objective This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH). Materials and Methods This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups. Results PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7. Conclusions Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients. .