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1.
N Engl J Med ; 382(9): 835-844, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32101665

RESUMO

Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.).


Assuntos
Mutação em Linhagem Germinativa , Transtornos do Crescimento/genética , Hipoglicemia/genética , Fator 1 Induzível por Hipóxia/deficiência , Mitocôndrias/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Expressão Gênica , Crescimento/genética , Humanos , Masculino , Metaboloma/genética , Metaboloma/fisiologia , Síndrome , Adulto Jovem
2.
Artigo em Inglês | MEDLINE | ID: mdl-31816837

RESUMO

Substance use among women is a major public health concern. This review article takes a developmental-relational approach to examine processes through which early relational trauma and violence in relationships may lead to substance use. We examine how early exposure to violence in relationships can impact neurological development, specifically through interference with physiological mechanisms (e.g., the hypothalamic-pituitary-adrenal axis), brain structure and functioning (e.g., the hippocampus and prefrontal cortex), and neuropsychological development (e.g., executive functioning and emotion regulation) across the lifespan. Further, we discuss the impact of exposure to violence on the development of relational capacity, including attachment, internal working models, and subsequent interpersonal relationships across the lifespan, and how these developmental pathways can lead to continued problematic substance use in women.


Assuntos
Mulheres Maltratadas/estatística & dados numéricos , Crescimento , Relações Interpessoais , Transtornos Relacionados ao Uso de Substâncias/etiologia , Violência/estatística & dados numéricos , Feminino , Humanos , Saúde Pública , Violência/psicologia
3.
Transplant Proc ; 51(9): 3059-3066, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31711584

RESUMO

BACKGROUND: There are limited data on predictors of growth after pediatric liver transplantation. METHODS: We reviewed the impact of graft type, ethnicity, and biliary complications (BC) on growth after pediatric liver transplantation (LT). We compared preoperative and 6-, 12-, and 24-month weight, height, and body mass index (BMI) percentiles between living donor (LD), deceased donor full-size (DD-full), and deceased donor split (DD-split) graft recipients. We also compared length of stay (LOS) between groups. RESULTS: We had 98 patients (DD-split: 32; DD-full: 43, LD: 23). The Median Pediatric End-stage Liver Disease (PELD) scores, exception points, albumin, bilirubin, failure to thrive, and presence of ascites were similar among groups. The DD-full group had the lowest preoperative percentiles in all categories and exceeded these at 24 months. The DD-split group was at preoperative percentiles at 24 months. The LD group had parallel weight curves compared to the DD-full group and exceeded only the preoperative weight percentile at 24 months. Black patients had the lowest percentiles in all categories (P < .01). The BC group caught up weight and BMI percentile at 24 months but had persistent decrease in height percentiles. Patients without BC exceeded preoperative height percentiles. The longer LOS group had lower height and BMI percentiles at 24 months; however, there was no statistical difference. CONCLUSION: DD-full and black patients seem to benefit the most from LT in terms of growth. BC seems to affect height percentiles. Patients with longer LOS had lower height and BMI percentiles (P>.05). Longer follow up and larger cohorts are necessary to improve the power of these findings.


Assuntos
Crescimento , Transplante de Fígado , Adolescente , Criança , Doença Hepática Terminal/cirurgia , Feminino , Humanos , Doadores Vivos , Masculino
4.
Am J Med Genet C Semin Med Genet ; 181(4): 611-626, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31730271

RESUMO

The nuclear factor one (NFI) site-specific DNA-binding proteins represent a family of transcription factors that are important for the development of multiple organ systems, including the brain. During brain development in mice, the expression patterns of Nfia, Nfib, and Nfix overlap, and knockout mice for each of these exhibit overlapping brain defects, including megalencephaly, dysgenesis of the corpus callosum, and enlarged ventricles, which implies a common but not redundant function in brain development. In line with these models, human phenotypes caused by haploinsufficiency of NFIA, NFIB, and NFIX display significant overlap, sharing neurodevelopmental deficits, macrocephaly, brain anomalies, and variable somatic overgrowth. Other anomalies may be present depending on the NFI gene involved. The possibility of variants in NFI genes should therefore be considered in individuals with intellectual disability and brain overgrowth, with individual NFI-related conditions being differentiated from one another by additional signs and symptoms. The exception is provided by specific NFIX variants that act in a dominant negative manner, as these cause a recognizable entity with more severe cognitive impairment and marked bone dysplasia, Marshall-Smith syndrome. NFIX duplications are associated with a phenotype opposite to that of haploinsufficiency, characterized by short stature, small head circumference, and delayed bone age. The spectrum of NFI-related disorders will likely be further expanded, as larger cohorts are assessed.


Assuntos
Crescimento/genética , Mutação , Fatores de Transcrição NFI/genética , Anormalidades Múltiplas/genética , Animais , Doenças do Desenvolvimento Ósseo/genética , Anormalidades Craniofaciais/genética , Duplicação Gênica , Transtornos do Crescimento/genética , Humanos , Camundongos , Displasia Septo-Óptica/genética , Síndrome
5.
J Acquir Immune Defic Syndr ; 82(4): 377-385, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31567725

RESUMO

BACKGROUND: Effects of prolonged nevirapine prophylaxis exposure on growth among HIV-exposed uninfected (HEU) infants are unknown. This study examines the impact of extended nevirapine prophylaxis from 6 weeks to 6 months on the growth of HEU infants followed for 18 months and also identifies correlates of incident wasting, stunting, underweight, and low head circumference in the HPTN 046 trial. METHODS: Intention-to-treat analysis examined the effect of extended nevirapine exposure on: weight-for-age Z-score, length-for-age Z-score, weight-for-length Z-score, and head circumference-for-age Z-score. Multivariable linear mixed-effects and Cox proportional hazard models were used to compare growth outcomes between the study arms and identify correlates of incident adverse growth outcomes, respectively. RESULTS: Compared to placebo, extended prophylactic nevirapine given daily from 6 weeks to 6 months did not affect growth in HEU breastfeeding (BF) infants over time (treatment × time: P > 0.05). However, overall growth declined over time (time effect: P < 0.01) when compared with WHO general population norms. Male sex was associated with higher risk of all adverse growth outcomes (P < 0.05), whereas short BF duration was associated with wasting (P = 0.03). Maternal antiretroviral therapy exposure was protective against underweight (P = 0.02). Zimbabwe tended to have worse growth outcomes especially stunting, compared to South Africa, Uganda and Tanzania (P < 0.05). CONCLUSIONS: It is reassuring that prolonged exposure to nevirapine for prevention-of-mother-to-child HIV transmission does not restrict growth. However, targeted interventions are needed to improve growth outcomes among at-risk HEU infants (i.e., male sex, short BF duration, lack of maternal antiretroviral therapy exposure, and resident in Zimbabwe).


Assuntos
Fármacos Anti-HIV/efeitos adversos , Desenvolvimento Infantil/efeitos dos fármacos , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Nevirapina/efeitos adversos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Feminino , Crescimento/efeitos dos fármacos , Humanos , Lactente , Gravidez
6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 750-756, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638573

RESUMO

Objective To prepare and characterize the somatostatin (SS) anti-idiotypic antibody of yolk (SS yolk Ab2 ) on the basis of successful preparation of neutralizing SS mAb1 2E7, and then to further probe the application of SS yolk Ab2 in promoting animal growth. Methods The egg-laying hens were immunized with the neutralizing SS mAb1 2E7. The eggs containing a high titer of SS yolk Ab2 were collected and the egg yolk was separated from the egg white. The SS yolk Ab2 in yolk solution was extracted by water dilution and acidification, and was purified by precipitating with cool ethanol. The titer, concentration and specificity of SS yolk Ab2 was determined by ELISA. The Ab2ß property of SS yolk Ab2 was determined by ELISA of competitive inhibition. The effect of SS yolk Ab2 on animal growth was experimented in the mice, chickens and fish. Results The SS yolk Ab2 had a titer of 1×10-5 and a concentration of 8 mg/mL. The SS yolk Ab2 could react with the rabbit antibody against SS, but not react with the rabbit antibody against growth hormone, insulin and gastrin. The immunoreaction between the SS yolk Ab2 and rabbit antibody against SS was inhibited by SS competitively. The SS yolk Ab2 could induce the mouse to produce SS Ab3 and the SS Ab3 could react with SS, which suggest that the SS yolk Ab2 was an Ab2ß. The SS yolk Ab2 was used to immunize the mice in different doses of 0.8 µg or 3.2 µg each mouse by subcutaneous injection, and to immunize the chickens in different doses of 0.8 µg or 3.2 µg each chicken through intramuscular injection, and to immunize the Doppelfish in doses of 3.2 µg each Doppelfish by immersing fishes in 2 L of sea water containing Ab2. The control animals were immunized with the same volume of physiological saline and by the same methods. One month later, the SS yolk Ab2 vaccine could increase body weight 33.5% and 37.0% in the mice, 25.6% and 34.1% in chickens, and 24.8% in the Doppelfish compared with the corresponding controls. Conclusion The SS yolk Ab2 was prepared successfully. It had a high titer, concentration and specificity. It is an Ab2ß as a vaccine can increase body weight of animals significantly by small-dose immunization only once.


Assuntos
Anticorpos Anti-Idiotípicos , Galinhas , Gema de Ovo , Somatostatina , Animais , Anticorpos Anti-Idiotípicos/análise , Anticorpos Anti-Idiotípicos/metabolismo , Gema de Ovo/química , Ensaio de Imunoadsorção Enzimática , Feminino , Peixes , Crescimento/fisiologia , Imunização , Camundongos
7.
Ann Hum Biol ; 46(4): 285-286, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31650872
8.
Integr Comp Biol ; 59(5): 1275-1280, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31553435

RESUMO

Until recently, the study of allometry has been mostly descriptive, and consisted of a diversity of methods for fitting regressions to bivariate or multivariate morphometric data. During the past decade, researchers have been developing methods to extract biological information from allometric data that could be used to deduce the underlying mechanisms that gave rise to the allometry. In addition, an increasing effort has gone into understanding the kinetics of growth and the regulatory mechanisms that control growth of the body and its component parts. The study of allometry and scaling has now become an exceptionally diverse field, with different investigators applying state of the art methods and concepts in evolution, developmental biology, cell biology, and genetics. Diversity has caused divergence, and we felt that although there is general agreement about the new goals for the study of allometry (understanding underlying mechanisms and how those evolve to produce different morphologies), progress is hindered by lack of coordination among the different approaches. We felt the time was right to bring these diverse practitioners together in a symposium to discuss their most recent work in the hope of forging new functional, conceptual, and collaborative connections among established and novice practitioners.


Assuntos
Tamanho Corporal , Crescimento , Animais , Evolução Biológica , Biologia Celular , Biologia do Desenvolvimento , Genética
9.
Phys Ther ; 99(12): 1712-1718, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31504925

RESUMO

BACKGROUND: Plumb line distances (PDs) are widely used in conservative clinical practice to evaluate the sagittal shape of the spine. OBJECTIVE: The objective was to assess the normative values of PDs in a large, healthy population in an age range representative of the adolescent population with spinal deformities, and to correlate it with x-ray measurements. DESIGN: This was a cross-sectional study. METHODS: Participants were 584 healthy individuals (341 females) with x-rays showing no spine deformities. The whole sample (OVERALL) was divided into 5 groups: 6 to 9 years old (n = 106); >10 years, Risser 0 with triradiate cartilage open (n = 129) or closed (n = 104); Risser 1 to 2 (n = 126); and Risser 3 to 5 (n = 119).PDs were taken by maintaining a tangent to the thoracic kyphosis apex at C7, T12, L3, and S2. Sagittal index (C7 + L3), and sagittal and coronal balances (C7 related to S2) were calculated. RESULTS: In OVERALL, PDs at C7, T12, L3, and S2 were 39.9 ± 16.7, 21.4 ± 15.3, 39.9 ± 15, 20.6 ± 17.0 mm, respectively. Sagittal index was 79.8 ± 26.8, sagittal balance was 19.3 ± 17 mm anterior to S2 plumb line; 13.5% had a coronal imbalance of 11.4 ± 5.4 mm to the right and 24.7% of 13.2 ± 6.0 mm to the left. C7 and L3 PDs, sagittal index, and sagittal balance were significantly lower in ages 6 to 9 compared to older patients in Risser 1 to 2 group. C7 and S2 PDs and sagittal index were significantly larger in males. Sagittal index correlated with thoracic kyphosis Cobb degrees (r = 0.47). LIMITATIONS: The participants were not randomly chosen from the general population; and they had an x-ray because of spine pathology suspicion. CONCLUSIONS: This study shows normative data to be used in clinical practice. Sagittal spinopelvic alignment has gained more and more importance in the last decades because of its high correlation to Health-Related Quality of Life scores in adults. 1.


Assuntos
Crescimento , Exame Físico/métodos , Coluna Vertebral/anatomia & histologia , Adolescente , Fatores Etários , Criança , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Exame Físico/instrumentação , Radiografia , Fatores Sexuais , Coluna Vertebral/diagnóstico por imagem
10.
PLoS One ; 14(8): e0220802, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393933

RESUMO

Studies from the social and health sciences have tended to view the household as the locus of access to and distribution of care, resources, monitoring and modeling for children's wellbeing. Obesity may present a special case for the study of investments in children, being a component of health for which more of certain inputs may not lead to better outcomes. We expanded on common measures of household structure in the child health literature by considering co-residence and relatedness of parents, grandparents, other relatives, and other children. Data were from a longitudinal sample of 6,700 children participating in the Early Childhood Longitudinal Study Kindergarten Class of 1998-99 (ECLS-K), the largest U.S. national dataset with measures of child anthropometrics and household structure at seven time-points over nine years. We used lagged survey-adjusted regressions to estimate associations between household structure and subsequent changes in children's weight between ages 5 and 14 years in terms of BMI gain and incident obesity. Adjusting for household structure more thoroughly, children living in households with two parents rather than one parent did not experience advantages in terms of less excess weight gain or lower incidence of obesity during elementary and middle school. Children living with a grandmother gained more weight than children not living with a grandmother. Living with siblings and with non-related adults was associated with less weight gain. These findings corroborate a scenario in which, for health problems associated with caloric surplus, classic household factors have more complex associations with child wellbeing.


Assuntos
Índice de Massa Corporal , Saúde da Criança/tendências , Características da Família , Adolescente , Criança , Desenvolvimento Infantil , Pré-Escolar , Ingestão de Energia , Crescimento , Humanos , Estudos Longitudinais , Obesidade/etiologia
11.
J Perinatol ; 39(10): 1406-1410, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31388118

RESUMO

BACKGROUND: NICU patients are commonly discharged home with nasogastric (NG) or gastrostomy (G-tube) feeding, but wide practice variation exists. The objective of this study was to evaluate feeding and growth outcomes and complications in NICU patients discharged home with NG or G-tube feeding. STUDY DESIGN: Retrospective cohort study of infants discharged from a Level IV NICU with an NG or G-tube who had follow up to 1 year. Clinical characteristics and outcomes were compared between groups. RESULTS: The study sample included 264 infants: 140 with NG and 124 with G-tube. More infants in the G-tube group (65%) still required tube feedings 12 months post-discharge than infants in the NG group (24%). Infants in the G-tube group had more tube-related ER visits than infants in the NG group. Growth outcomes did not differ. CONCLUSION: Home NG feeding may be a safe alternative to a surgically placed G-tube in select NICU patients.


Assuntos
Nutrição Enteral , Gastrostomia , Intubação Gastrointestinal , Estudos de Coortes , Feminino , Gastrostomia/efeitos adversos , Crescimento , Humanos , Lactente , Recém-Nascido/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Intubação Gastrointestinal/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos
12.
PLoS One ; 14(8): e0220441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31390356

RESUMO

This study was performed to investigate the effects of dietary inclusion of 20% rapeseed meal (RSM) as an alternative to soybean meal (SBM) in a three-month feeding experiment with growing finishing pigs. Dietary alteration affected growth performance, several carcass traits and transcriptional responses in the skeletal muscle, but did not affect measured meat quality traits. In general, pigs fed the RSM test diet exhibited reduced growth performance compared to pigs on SBM control diet. Significant transcriptional changes in the skeletal muscle of growing pigs fed RSM diet were likely the consequence of an increased amount of fiber and higher polyunsaturated fatty acids, and presence of bioactive phytochemicals, such as glucosinolates. RNAseq pipeline using Tophat2-Cuffdiff identified 57 upregulated and 63 downregulated genes in RSM compared to SBM pigs. Significantly enriched among downregulated pathways was p53-mediated signalling involved in cellular proliferation, while activation of negative growth regulators (IER5, KLF10, BTG2, KLF11, RETREG1, PRUNE2) in RSM fed pigs provided further evidence for reduced proliferation and increased cellular death, in accordance with the observed reduction in performance traits. Upregulation of well-known metabolic controllers (PDK4, UCP3, ESRRG and ESRRB), involved in energy homeostasis (glucose and lipid metabolism, and mitochondrial function), suggested less available energy and nutrients in RSM pigs. Furthermore, several genes supported more pronounced proteolysis (ABTB1, OTUD1, PADI2, SPP1) and reduced protein synthesis (THBS1, HSF4, AP1S2) in RSM muscle tissue. In parallel, higher levels of NR4A3, PDK4 and FGF21, and a drop in adropin, ELOVL6 and CIDEC/FSP27 indicated increased lipolysis and fatty acid oxidation, reflective of lower dressing percentage. Finally, pigs exposed to RSM showed greater expression level of genes responsive to oxidative stress, indicated by upregulation of GPX1, GPX2, and TXNIP.


Assuntos
Ração Animal/normas , Brassica napus , Carne/normas , Músculo Esquelético/metabolismo , Transcriptoma/genética , Animais , Economia , Regulação da Expressão Gênica , Crescimento , Estresse Oxidativo/genética , Suínos
13.
Pediatr Pulmonol ; 54(11): 1722-1734, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397120

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the most common complications in premature infants. Since inflammation plays a crucial role in the pathogenesis of BPD, anti-inflammatory drugs, such as corticosteroids, have long been the focus of prevention research. In this meta-analysis, we aim to explore the long-term effects of the intratracheal administration of corticosteroids (IAC) in preventing BPD. METHODS: EMBASE, MEDLINE, the Cochrane Library, Web of Science, CINAHL, Clinicaltrials.gov, the ISRCTN registry, and gray literature were searched to identify randomized controlled trials (RCTs) that evaluated the long-term effects of IAC for the prevention of BPD in premature infants. RESULTS: Five RCTs (n = 1515) were eligible for further analysis. The meta-analysis revealed that the incidence of neurodevelopmental impairment (NDI) did not significantly differ between the IAC group and the control group (relative risk [RR] 0.9, 95% confidence interval [CI] 0.79 to 1.03, P = .14). There was no significant reduction in long-term mortality (RR, 1.13; 95% CI, 0.9 to 1.41; P = .3) or the incidence of rehospitalization (RR, 0.99; 95% CI, 0.89 to 1.09, P = .82). No significant differences were observed between the IAC group and the control group with regard to height, weight and head circumference at the age of 18 to 36 months of postmenstrual age (PMA) (mean difference [MD], 0.14; 95% CI, -0.26 to 0.54, P = .48). CONCLUSIONS: Our study suggests that IAC in preterm infants does not have significant long-term benefits or adverse outcomes. However, before routine use, well-designed studies and studies involving large sample sizes are needed to confirm the pharmacokinetics and long-term effects of IAC.


Assuntos
Corticosteroides/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Displasia Broncopulmonar/prevenção & controle , Recém-Nascido Prematuro , Administração por Inalação , Corticosteroides/efeitos adversos , Corticosteroides/farmacocinética , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacocinética , Displasia Broncopulmonar/complicações , Crescimento , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Transtornos do Neurodesenvolvimento/etiologia , Readmissão do Paciente
14.
Ann Hum Biol ; 46(5): 415-424, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31460800

RESUMO

Background: Cardiometabolic disease is associated with chronic low-grade inflammation. While low birthweight, childhood stunting and rapid weight gain predict higher adult high-sensitivity C-reactive protein (hs-CRP) concentrations, associations between childhood infections and adulthood CRP are inconsistent.Aim: To assess the associations between sanitation, diarrhoea and a combined score of both from birth to age 2 years and hs-CRP at age 18 years, independently of early life nutrition and adult adiposity.Subjects and methods: This study collected data on sanitation and diarrhoea episodes from birth to 2 years on 756 participants of the Birth-to-Twenty Plus cohort, a birth cohort initiated in South Africa in 1990, and calculated a combined score of both variables. Anthropometry was measured at 2 years and 18 years and hs-CRP at 18 years.Results: Of the participants, 29.5% had no access to indoor flush sanitation and 38.2% experienced ≥1 diarrhoea episode between birth and 2 years. Not having access to indoor flush sanitation and experiencing ≥1 diarrhoea episodes were associated with 1.50 mg/L and 1.52 mg/L higher hs-CRP, respectively. Prevalence of both burdens in infancy was associated with a 2.18 mg/L higher hs-CRP.Conclusion: In this population, poor sanitation and diarrhoea in early life predict elevated CRP in young adulthood, independently of early life nutrition and adiposity.


Assuntos
Adiposidade , Proteína C-Reativa/metabolismo , Diarreia/epidemiologia , Crescimento , Saneamento/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adolescente , Pré-Escolar , Estudos de Coortes , Humanos , Lactente , África do Sul/epidemiologia , Adulto Jovem
15.
Hypertens Pregnancy ; 38(4): 208-216, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364410

RESUMO

Objective: The study investigates how IVC and ET affect hypertensive phenotype in ISIAH rats. Methods: ISIAH rats born as the result of ET and IVC were compared with naturally conceived controls. Results: Embryo transfer from hypertensive ISIAH rats to normotensive recipient dams caused lower SBP and DBP in the female offspring. When ET was accompanied with in vitro culture in R1ECM, not only the female offspring, but also males demonstrated alleviation of hypertension. Conclusions: IVC at the preimplantation embryo stage affected the manifestation of hypertension in the adult ISIAH offspring.


Assuntos
Técnicas de Cultura Embrionária , Transferência Embrionária , Hipertensão/etiologia , Animais , Animais Recém-Nascidos , Pressão Sanguínea , Peso Corporal , Feminino , Crescimento , Masculino , Gravidez , Ratos , Reflexo de Endireitamento
16.
N Engl J Med ; 381(1): 25-35, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269546

RESUMO

BACKGROUND: Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification. METHODS: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia. A total of 35 children were enrolled in four sequential cohorts to receive vosoritide at a once-daily subcutaneous dose of 2.5 µg per kilogram of body weight (8 patients in cohort 1), 7.5 µg per kilogram (8 patients in cohort 2), 15.0 µg per kilogram (10 patients in cohort 3), or 30.0 µg per kilogram (9 patients in cohort 4). After 6 months, the dose in cohort 1 was increased to 7.5 µg per kilogram and then to 15.0 µg per kilogram, and in cohort 2, the dose was increased to 15.0 µg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses. At the time of data cutoff, the 24-month dose-finding study had been completed, and 30 patients had been enrolled in an ongoing long-term extension study; the median duration of follow-up across both studies was 42 months. RESULTS: During the treatment periods in the dose-finding and extension studies, adverse events occurred in 35 of 35 patients (100%), and serious adverse events occurred in 4 of 35 patients (11%). Therapy was discontinued in 6 patients (in 1 because of an adverse event). During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed with vosoritide up to a dose of 15.0 µg per kilogram, and a sustained increase in the annualized growth velocity was observed at doses of 15.0 and 30.0 µg per kilogram for up to 42 months. CONCLUSIONS: In children with achondroplasia, once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that appeared generally mild. Treatment resulted in a sustained increase in the annualized growth velocity for up to 42 months. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov numbers, NCT01603095, NCT02055157, and NCT02724228.).


Assuntos
Acondroplasia/tratamento farmacológico , Crescimento/efeitos dos fármacos , Peptídeo Natriurético Tipo C/análogos & derivados , Osteogênese/efeitos dos fármacos , Acondroplasia/fisiopatologia , Adolescente , Biomarcadores/análise , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Colágeno/sangue , GMP Cíclico/urina , Relação Dose-Resposta a Droga , Feminino , Gráficos de Crescimento , Humanos , Injeções Subcutâneas , Masculino , Peptídeo Natriurético Tipo C/administração & dosagem , Peptídeo Natriurético Tipo C/efeitos adversos , Peptídeo Natriurético Tipo C/uso terapêutico
17.
Anim Sci J ; 90(9): 1229-1238, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31264347

RESUMO

This study evaluated the effects of berberine on growth performance, immunity, haematological parameters, antioxidant capacity, and the expression of immune response-related genes in lipopolysaccharide (LPS)-challenged broilers. We assigned 120 one-day-old male broilers (Ross 308) to two treatment groups; each group included two subgroups, each of which included six replicates of five birds per replicate. The experiment used a 2 × 2 factorial arrangement with berberine treatment (0 or 60 mg/kg dietary) and challenge status [injection of saline (9 g/L w/v) or LPS (1.5 mg/kg body weight)] as the main factors. On days 14, 16, 18 and 20, broilers were intraperitoneally injected with LPS or physiological saline. Blood and liver samples were collected on day 21. Dietary berberine supplementation significantly alleviated the compromised average daily gain and average daily feed intake (p < 0.05) caused by LPS. The LPS challenge led to increased lymphocyte and white blood cell (WBC) counts, malondialdehyde (serum and liver) content, and immunoglobulin G and M, tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) expression (p < 0.05) and significantly reduced serum total superoxide dismutase (T-SOD) activity (p < 0.05). Dietary berberine significantly mitigated the LPS-induced decreases in the mRNA expression of nuclear factor-kappa B (NF-κB), TNF-α, IL-1ß, inducible nitrite synthase and cyclooxygenase-2 (p < 0.05) in the liver. In conclusion, berberine supplementation has a positive effect on LPS challenge, which may be related to the increase in antioxidant enzyme activity and inhibition of both NF-κB signalling and the expression of inflammatory mediators.


Assuntos
Antioxidantes/uso terapêutico , Berberina/uso terapêutico , Dieta/veterinária , Crescimento/efeitos dos fármacos , Inflamação/veterinária , Lipopolissacarídeos/imunologia , Animais , Elementos de Resposta Antioxidante , Antioxidantes/metabolismo , Berberina/metabolismo , Galinhas , Suplementos Nutricionais , Inflamação/dietoterapia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Masculino , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Doenças das Aves Domésticas/dietoterapia
18.
Phys Rev Lett ; 122(23): 238101, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31298905

RESUMO

Metabolism and evolution are closely connected: if a mutation incurs extra energetic costs for an organism, there is a baseline selective disadvantage that may or may not be compensated for by other adaptive effects. A long-standing, but to date unproven, hypothesis is that this disadvantage is equal to the fractional cost relative to the total resting metabolic expenditure. We validate this result from physical principles through a general growth model and show it holds to excellent approximation for experimental parameters drawn from a wide range of species.


Assuntos
Metabolismo Energético , Crescimento , Modelos Biológicos , Seleção Genética
19.
Anim Sci J ; 90(9): 1099-1110, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270894

RESUMO

Immunoglobulin (Ig) is the one of the main anti-infective components of blood, colostrum and breast milk. It is the unique glycoprotein that defends the body from harmful bacteria, viruses and other environmental pathogens by either binding to them or by forming an encapsulating barrier. The expansion of antimicrobial and immunomodulatory products from natural sources for dietary supplementation in both animals and humans is an ever growing and thriving area of research. Purified Ig from sheep serum (ovine serum Ig) is one such candidate product. Recent work has shown the various biological effects of oral Ig in different animal models including its effect on growth, immunity, intestinal growth and gut barrier function. The objective of this paper is to review the results of recent studies demonstrating the effects of oral Ig in both pathogenic and non-pathogenic animal models and to suggest a possible mechanism of its action. Overall, purified oral Ig improves growth of healthy (and challenged) rats and defends against enteric infection by immunomodulation, mucin protein and/or modification of commensal microbial composition. The findings contribute to knowledge of how orally administered ovine Ig can influence and enhance key indicators of gut function and overall growth performance in an animal model.


Assuntos
Bem-Estar do Animal , Imunoglobulinas/farmacologia , Imunoglobulinas/uso terapêutico , Administração Oral , Doenças dos Animais/prevenção & controle , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Imunoglobulinas/administração & dosagem , Microbiota/efeitos dos fármacos , Ratos , Ovinos
20.
Nutr Hosp ; 36(4): 777-785, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31271292

RESUMO

Introduction: Introduction: several investigations have identified breastfeeding as a protective factor for rapid infant weight gain and childhood obesity while other studies have found that this protective effect could be the result of confounding factors. Objectives: to assess the associations between lactation practices (breast-fed vs formula-fed infants) during the introduction of complementary food period, as well as the following: a) patterns of food intake; and b) trajectories of growth at six, nine and 12 months (z-score of weight, height and body mass index [BMI] and changes in these z-scores from six to 12 months). Methods: two hundred and three infants randomly selected from Spanish Primary Health Centres were measured. Parents recorded all infant's food consumption for three days (g/day). Linear regression models were applied. Results: breast-fed infants had a lower intake of cereals, fruit baby food, vegetables with meat/fish and a total intake of food compared to formula-fed infants at nine months of age. After adjusting for sex, parental education and total food intake, breastfed children continued to have lower intake of cereals (-5.82, 95% CI: -9.22, -2.43), and lower total food intake (-301.23, 95% CI: -348.50, -253.96). Breast-fed infants had a lower change in z-score of weight, height and BMI from six to 12 months of age and these differences remained when adjusting for all confounders. Conclusions: formula-fed infants during the complementary feeding period have a higher food intake and show higher rates of rapid infant weight gain compared to breast-fed infants. These differences in growth trajectories depending on breastfeeding maintenance and food intake during early life must be considered in adiposity risk evaluation.


Assuntos
Aleitamento Materno , Comportamento Alimentar , Crescimento/fisiologia , Alimentos Infantis , Fórmulas Infantis , Fatores Etários , Estatura , Índice de Massa Corporal , Registros de Dieta , Grão Comestível , Escolaridade , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pais/educação , Ganho de Peso
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