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2.
BMC Pediatr ; 21(1): 308, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243738

RESUMO

BACKGROUND: Less than 2% of overweight children and adolescents in Switzerland can participate in multi-component behaviour changing interventions (BCI), due to costs and lack of time. Stress often hinders positive health outcomes in youth with obesity. Digital health interventions, with fewer on-site visits, promise health care access in remote regions; however, evidence for their effectiveness is scarce. METHODS: This randomized controlled not blinded trial (1:1) was conducted in a childhood obesity center in Switzerland. Forty-one youth aged 10-18 years with body mass index (BMI) > P.90 with risk factors or co-morbidities or BMI > P.97 were recruited. During 5.5 months, the PathMate2 group (PM) received daily conversational agent counselling via mobile app, combined with standardized counselling (4 on-site visits). Controls (CON) participated in a BCI (7 on-site visits). We compared the outcomes of both groups after 5.5 (T1) and 12 (T2) months. Primary outcome was reduction in BMI-SDS (BMI standard deviation score: BMI adjusted for age and sex). Secondary outcomes were changes in body fat and muscle mass (bioelectrical impedance analysis), waist-to-height ratio, physical capacities (modified Dordel-Koch-Test), blood pressure and pulse. Additionally, we hypothesized that less stressed children would lose more weight. Thus, children performed biofeedback relaxation exercises while stress parameters (plasma cortisol, stress questionnaires) were evaluated. RESULTS: At intervention start median BMI-SDS of all patients (18 PM, 13 CON) was 2.61 (obesity > + 2SD). BMI-SDS decreased significantly in CON at T1, but not at T2, and did not decrease in PM during the study. Muscle mass, strength and agility improved significantly in both groups at T2; only PM reduced significantly their body fat at T1 and T2. Average daily PM app usage rate was 71.5%. Cortisol serum levels decreased significantly after biofeedback but with no association between stress parameters and BMI-SDS. No side effects were observed. CONCLUSIONS: Equally to BCI, PathMate2 intervention resulted in significant and lasting improvements of physical capacities and body composition, but not in sustained BMI-SDS decrease. This youth-appealing mobile health intervention provides an interesting approach for youth with obesity who have limited access to health care. Biofeedback reduces acute stress and could be an innovative adjunct to usual care.


Assuntos
Obesidade Pediátrica , Telemedicina , Adolescente , Índice de Massa Corporal , Criança , Humanos , Sobrepeso , Obesidade Pediátrica/terapia , Suíça
3.
Sci Rep ; 9(1): 2201, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30778093

RESUMO

The resilience of corals to ocean acidification has been proposed to rely on regulation of extracellular calcifying medium pH (pHECM), but few studies have compared the capacity of coral species to control this parameter at elevated pCO2. Furthermore, exposure to light and darkness influences both pH regulation and calcification in corals, but little is known about its effect under conditions of seawater acidification. Here we investigated the effect of acidification in light and darkness on pHECM, calcifying cell intracellular pH (pHI), calcification, photosynthesis and respiration in three coral species: Stylophora pistillata, Pocillopora damicornis and Acropora hyacinthus. We show that S. pistillata was able to maintain pHECM under acidification in light and darkness, but pHECM decreased in P. damicornis and A. hyacinthus to a much greater extent in darkness than in the light. Acidification depressed calcifying cell pHI in all three species, but we identified an unexpected positive effect of light on pHI. Calcification rate and pHECM decreased together under acidification, but there are inconsistencies in their relationship indicating that other physiological parameters are likely to shape how coral calcification responds to acidification. Overall our study reveals interspecies differences in coral regulation of pHECM and pHI when exposed to acidification, influenced by exposure to light and darkness.


Assuntos
Antozoários/fisiologia , Concentração de Íons de Hidrogênio , Fotoperíodo , Água do Mar/análise , Água do Mar/química , Animais , Biomassa , Calcificação Fisiológica , Carbonatos , Respiração Celular , Recifes de Corais , Monitoramento Ambiental , Fotossíntese
4.
Sci Rep ; 7(1): 11210, 2017 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-28894174

RESUMO

Calcareous octocorals are ecologically important calcifiers, but little is known about their biomineralization physiology, relative to scleractinian corals. Many marine calcifiers promote calcification by up-regulating pH at calcification sites against the surrounding seawater. Here, we investigated pH in the red octocoral Corallium rubrum which forms sclerites and an axial skeleton. To achieve this, we cultured microcolonies on coverslips facilitating microscopy of calcification sites of sclerites and axial skeleton. Initially we conducted extensive characterisation of the structural arrangement of biominerals and calcifying cells in context with other tissues, and then measured pH by live tissue imaging. Our results reveal that developing sclerites are enveloped by two scleroblasts and an extracellular calcifying medium of pH 7.97 ± 0.15. Similarly, axial skeleton crystals are surrounded by cells and a calcifying medium of pH 7.89 ± 0.09. In both cases, calcifying media are more alkaline compared to calcifying cells and fluids in gastrovascular canals, but importantly they are not pH up-regulated with respect to the surrounding seawater, contrary to what is observed in scleractinians. This points to a potential vulnerability of this species to decrease in seawater pH and is consistent with reports that red coral calcification is sensitive to ocean acidification.


Assuntos
Antozoários/fisiologia , Calcificação Fisiológica , Microscopia Intravital , Animais , Concentração de Íons de Hidrogênio
5.
Proc Biol Sci ; 284(1847)2017 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-28100813

RESUMO

Reef coral calcification depends on regulation of pH in the internal calcifying fluid (CF) in which the coral skeleton forms. However, little is known about calcifying fluid pH (pHCF) regulation, despite its importance in determining the response of corals to ocean acidification. Here, we investigate pHCF in the coral Stylophora pistillata in seawater maintained at constant pH with manipulated carbonate chemistry to alter dissolved inorganic carbon (DIC) concentration, and therefore total alkalinity (AT). We also investigate the intracellular pH of calcifying cells, photosynthesis, respiration and calcification rates under the same conditions. Our results show that despite constant pH in the surrounding seawater, pHCF is sensitive to shifts in carbonate chemistry associated with changes in [DIC] and [AT], revealing that seawater pH is not the sole driver of pHCF Notably, when we synthesize our results with published data, we identify linear relationships of pHCF with the seawater [DIC]/[H+] ratio, [AT]/ [H+] ratio and [[Formula: see text]]. Our findings contribute new insights into the mechanisms determining the sensitivity of coral calcification to changes in seawater carbonate chemistry, which are needed for predicting effects of environmental change on coral reefs and for robust interpretations of isotopic palaeoenvironmental records in coral skeletons.


Assuntos
Antozoários/fisiologia , Calcificação Fisiológica , Carbonatos/química , Água do Mar/química , Animais , Recifes de Corais , Concentração de Íons de Hidrogênio
6.
Oncogene ; 35(48): 6189-6202, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27157613

RESUMO

ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC. TZ and lapatinib ability to block extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase (PI3K)/AKT in sensitive cells inhibits c-Myc activation, which results in upregulation of miR-16. Forced expression of miR-16 inhibited in vitro proliferation in BC and GC cells, both sensitive and resistant to TZ and lapatinib, as well as in a preclinical BC model resistant to these agents. This reveals miR-16 role as tumor suppressor in ErbB-2-positive BC and GC. Using genome-wide expression studies and miRNA target prediction algorithms, we identified cyclin J and far upstream element-binding protein 1 (FUBP1) as novel miR-16 targets, which mediate miR-16 antiproliferative effects. Supporting the clinical relevance of our results, we found that high levels of miR-16 and low or null FUBP1 expression correlate with TZ response in ErbB-2-positive primary BCs. These findings highlight a potential role of miR-16 and FUBP1 as biomarkers of sensitivity to TZ therapy. Furthermore, we revealed miR-16 as an innovative therapeutic agent for TZ- and lapatinib-resistant ErbB-2-positive BC and GC.


Assuntos
Neoplasias da Mama/genética , Ciclinas/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Quinazolinas/farmacologia , Neoplasias Gástricas/genética , Trastuzumab/farmacologia , Regiões 3' não Traduzidas , Animais , Antineoplásicos/farmacologia , Sítios de Ligação , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genes Supressores de Tumor , Humanos , Lapatinib , Masculino , Camundongos , Modelos Biológicos , Regiões Promotoras Genéticas , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , Proteínas de Ligação a RNA , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo
7.
Science ; 349(6243): aac4722, 2015 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-26138982

RESUMO

The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems­and the goods and services they provide­for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario­consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2°C­is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate.


Assuntos
Organismos Aquáticos , Dióxido de Carbono , Ecossistema , Aquecimento Global , Efeito Estufa , Animais , Aquicultura , Saúde , Humanos , Oceanos e Mares , Risco , Viagem
8.
Nat Commun ; 6: 7368, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26067341

RESUMO

Ocean acidification causes corals to calcify at reduced rates, but current understanding of the underlying processes is limited. Here, we conduct a mechanistic study into how seawater acidification alters skeletal growth of the coral Stylophora pistillata. Reductions in colony calcification rates are manifested as increases in skeletal porosity at lower pH, while linear extension of skeletons remains unchanged. Inspection of the microstructure of skeletons and measurements of pH at the site of calcification indicate that dissolution is not responsible for changes in skeletal porosity. Instead, changes occur by enlargement of corallite-calyxes and thinning of associated skeletal elements, constituting a modification in skeleton architecture. We also detect increases in the organic matrix protein content of skeletons formed under lower pH. Overall, our study reveals that seawater acidification not only causes decreases in calcification, but can also cause morphological change of the coral skeleton to a more porous and potentially fragile phenotype.


Assuntos
Antozoários/metabolismo , Calcificação Fisiológica , Dióxido de Carbono/química , Água do Mar/química , Animais , Proteínas da Matriz Extracelular/metabolismo , Concentração de Íons de Hidrogênio , Porosidade
9.
Sci Rep ; 4: 5207, 2014 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-24903088

RESUMO

Ocean acidification driven by rising levels of CO2 impairs calcification, threatening coral reef growth. Predicting how corals respond to CO2 requires a better understanding of how calcification is controlled. Here we show how spatial variations in the pH of the internal calcifying fluid (pHcf) in coral (Stylophora pistillata) colonies correlates with differential sensitivity of calcification to acidification. Coral apexes had the highest pHcf and experienced the smallest changes in pHcf in response to acidification. Lateral growth was associated with lower pHcf and greater changes with acidification. Calcification showed a pattern similar to pHcf, with lateral growth being more strongly affected by acidification than apical. Regulation of pHcf is therefore spatially variable within a coral and critical to determining the sensitivity of calcification to ocean acidification.


Assuntos
Ácidos/química , Antozoários/fisiologia , Calcificação Fisiológica , Dióxido de Carbono/química , Água do Mar/química , Animais , Recifes de Corais , Homeostase , Concentração de Íons de Hidrogênio , Oceanos e Mares
10.
Int J Obes (Lond) ; 37(4): 493-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23147116

RESUMO

OBJECTIVE: The aim was to analyze the effectiveness of treatment concerning obesity-associated comorbidities in clinical practice. METHODS: A total of 11,681 overweight children with ≥ 6-month follow-up treated at 175 centers specialized in pediatric obesity care in Central Europe were included in this analysis (mean body mass index (BMI) 29.0 ± 5.6 kg m(-)(2), standard deviation score body mass index (SDS-BMI) 2.48 ± 0.54, 45% boys, age 11.4 ± 2.8 years). The changes of weight status, blood pressure, fasting lipids and glucose, and oral glucose tolerance tests were documented by standardized prospective quality documentation software (APV). RESULTS: After follow-up of in median 1.2 (interquartile range 0.9-2.2) years, a mean reduction of -0.15 SDS-BMI was achieved. The prevalence of prehypertension (37->33%) and hypertension (17->12%) decreased, while prevalences of triglycerides >150 mg dl(-1) (22->21%), low-density-lipoprotein-cholesterol >130 mg dl(-1) (15->14%), impaired fasting glucose (6->6%) and impaired glucose tolerance (9->8%) remained stable. Drug treatment according to cutoffs recommended in European obesity guidelines were not frequently indicated (hypertension: 10%; dyslipidemia: 1%, type 2 diabetes <1%). None of the children with dyslipidemia received lipid-lowering drugs and only 1.4% of the children with hypertension were treated with antihypertensive drugs. CONCLUSIONS: Achieving sufficient weight loss to improve obesity associated comorbidities was difficult in clinical practice. Drug treatment of hypertension, dyslipidemia and type 2 diabetes was rarely performed even if it was indicated only in a minority of the overweight children. Future analyses should identify reasons for this insufficient drug treatment of comorbidities and analyze whether the benchmarking processes of APV improve medical care of childhood obesity.


Assuntos
Serviços de Saúde do Adolescente , Doenças Cardiovasculares/epidemiologia , Serviços de Saúde da Criança , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Obesidade/epidemiologia , Adolescente , Adulto , Áustria/epidemiologia , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Criança , Pré-Escolar , Comorbidade , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Lipídeos/sangue , Estudos Longitudinais , Masculino , Obesidade/sangue , Obesidade/tratamento farmacológico , Prevalência , Fatores de Risco , Suíça/epidemiologia
11.
Rev. argent. mastología ; 30(107): 119-125, jul. 2011. graf
Artigo em Espanhol | LILACS | ID: lil-638472

RESUMO

En este studio retrospective se evaluó nuestra experiencia en punciones con aguja fina (P.A.A.F.) con y sin control ecográfico en el Servicio de Ginecología y Patología Mamaria del Hospital Juan A. Fernández. El período analizado comprende entre los años 2000 y 2009. Hemos realizado un total de 3.420 punciones en un total de 2.858 pacientes, de las mismas 2.052 punciones se han realizado sin control ecográfico (tumores palpables) y 1.368 punciones fueron efectuadas con control ecográfico. En todos los casos se contó con la presencia del patólogo para el análisis del material extraído. En 3.420 punciones realizadas por nuestro equipo tuvimos los siguientes resultados: 840 positivos, 2.030 negativos, 75 insuficientes, y 370 material no representativo. Hemos incluido en nuestro material todo tumor palpable al examen clínico, imágenes ecográficas y adenopatías palpables por imaginología. La punción con aguja fina es un instrumento valioso en la conducta terapéutica de los nódulos mamarios. En los casos con imágenes presuntamente benignas la punción con aguja fina con resultado negativo nos permite confirmar los hallazgos por imaginología. Por el contrario, frente a un resultado positivo nos permite planificar la estratégica quirúrgica. Destacamos que la P.A.A.F es un método eficaz de bajo costo y muy pocas complicaciones para la paciente, lo cual nos permite obtener un resultado confiable en el momento. Por tal motivo en nuestra institución la P.A.A.F es la modalidad diagnóstica inicial de elección.


Assuntos
Biópsia por Agulha Fina , Biologia Celular , Punções
12.
Artigo em Inglês | MEDLINE | ID: mdl-21281736

RESUMO

We analysed the soluble organic matrix (SOM) of two biominerals formed by the same organism but differing by their morphological characteristics: the axial skeleton and the sclerites of Corallium rubrum. The results of 1D SDS-PAGE electrophoresis show for the two biominerals that SOM proteins bands have similar apparent molecular weight but differ in quantity. Further analysis by 2D electrophoresis reveals each protein band as a line of spots with different isoelectric points. Our results suggest that each SOM protein band consists of a mix of proteins and/or one unique protein with post-translational modifications. By immunohistochemistry, we show that antibodies raised against the SOM of axial skeleton and sclerites label the SOM of the two biominerals but also label the insoluble organic matrix suggesting the presence of common epitopes between the two biominerals and the two organic fractions.


Assuntos
Antozoários/química , Calcificação Fisiológica , Animais , Antozoários/anatomia & histologia , Antozoários/fisiologia , Proteínas/análise , Proteínas/química
13.
Rev. argent. mastología ; 29(103): 121-133, jul. 2010. tab
Artigo em Espanhol | LILACS | ID: lil-578021

RESUMO

Introducción: la posibilidad de identificar pacientes HER2 positivo y poder ofrecerles una terapia específica ha cambiado el pronóstico y la evolución de las mismas, es por ello que la determinación de sobreexpresión de HER2 es una factor clave para la toma de decisiones en el tratamiento del cáncer de mama. Objetivo: recolectar datos locales de la incidencia de la sobreexpresión de HER2 en la población con cáncer de mama de reciente diagnóstico y datos de anatomía patológica y la relación de los mismos con la sobreexpresión de HER2. Materiales y método: estudio epidemiológico que recolecta datos de las fichas de anatomía patológica y de las historias clínicas de pacientes con cáncer de mama operadas entre agosto de 2006 y agosto de 2007. De las biopsias previamente realizadas de rutina en pacientes operadas, se tomó un extendido para la determinación de HER2 por inmunohistoquímica (IHQ) con un anticuerpo policlonal anti HER2 (Dako), recuperación antigénica en microondas, sistema de detección En Vision (Dako) y revelado con diaminobenzidina. Para interpretar los resultados se usó el score de ASCO/CAP. Resultados: ingresaron 342 pacientes, HER negativo, 285 pacientes (83%); dudoso, 19 pacientes (6%); y HER2 positivo, 38 pacientes (11%). La edad promedio fue de 63,7 años. Se compararon las características clínicas y anatomopatológicas de ambas poblaciones (Tabla I). Conclusiones: la incidencia de HER2 positivo fue inferior (11%) a las reportadas en otras series, probablemente influida por el tamaño de la muestra o por el estadio inicial de las pacientes.


Assuntos
Neoplasias da Mama , Estudos Epidemiológicos
14.
Rev. argent. mastología ; 29(103): 121-133, jul. 2010. tab
Artigo em Espanhol | BINACIS | ID: bin-125382

RESUMO

Introducción: la posibilidad de identificar pacientes HER2 positivo y poder ofrecerles una terapia específica ha cambiado el pronóstico y la evolución de las mismas, es por ello que la determinación de sobreexpresión de HER2 es una factor clave para la toma de decisiones en el tratamiento del cáncer de mama. Objetivo: recolectar datos locales de la incidencia de la sobreexpresión de HER2 en la población con cáncer de mama de reciente diagnóstico y datos de anatomía patológica y la relación de los mismos con la sobreexpresión de HER2. Materiales y método: estudio epidemiológico que recolecta datos de las fichas de anatomía patológica y de las historias clínicas de pacientes con cáncer de mama operadas entre agosto de 2006 y agosto de 2007. De las biopsias previamente realizadas de rutina en pacientes operadas, se tomó un extendido para la determinación de HER2 por inmunohistoquímica (IHQ) con un anticuerpo policlonal anti HER2 (Dako), recuperación antigénica en microondas, sistema de detección En Vision (Dako) y revelado con diaminobenzidina. Para interpretar los resultados se usó el score de ASCO/CAP. Resultados: ingresaron 342 pacientes, HER negativo, 285 pacientes (83%); dudoso, 19 pacientes (6%); y HER2 positivo, 38 pacientes (11%). La edad promedio fue de 63,7 años. Se compararon las características clínicas y anatomopatológicas de ambas poblaciones (Tabla I). Conclusiones: la incidencia de HER2 positivo fue inferior (11%) a las reportadas en otras series, probablemente influida por el tamaño de la muestra o por el estadio inicial de las pacientes.


Assuntos
Neoplasias da Mama , Estudos Epidemiológicos
15.
Int J Obes (Lond) ; 34(10): 1468-74, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20531349

RESUMO

OBJECTIVE: Comorbidities of childhood obesity challenge health-care systems in Europe. Further, there is a lack of population-specific prevalence data and diagnostic strategies available, especially for obesity-related disturbances of liver function. Therefore, the prevalence of elevated liver enzymes and their relationship to biological parameters were studied in a large pediatric obesity cohort. METHODS: In 111 specialized pediatric obesity centers in Germany, Austria and Switzerland, 16,390 children and adolescents (age 12.4±2.6 years, 58% boys) were categorized as overweight (body mass index (BMI) >90th percentile) and obese (>97th percentile) and studied for related comorbidities, especially nonalcoholic fatty liver disease (NAFLD; as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >50 U l(-1)). Data were collected using a standardized software program (APV) for longitudinal multicenter documentation. Pseudonymized data were transmitted for central statistical analysis. RESULTS: In this pediatric cohort, 16% of the study population was overweight, 46% obese and 35% extremely obese (>99.5th percentile extreme obesity (Xob)). NAFLD was present in 11% of the study population, but predominantly in boys (boys vs girls; 14.4:7.4%; P<0.001), in Xob (obese vs Xob; 9.5:17.0%; P<0.001) and in older age (< 12 vs ≥12 years; 8:12%; P<0.001; adjusted for BMI). ALT >50 U l(-1) was significantly associated with fasting insulin and BMI-SDS. In multiple logistic regression models, Xob and male gender were strongly associated with NAFLD (odds ratio Xob vs normal weight=3.2; boys vs girls OR=2.3). CONCLUSION: In a large cohort of overweight and obese European children and adolescents, markers of nonalcoholic liver disease, especially ALT, are frequent and predicted by Xob and male gender. The results underline the epidemiological dimension of this obesity-related morbidity even in childhood. Therefore, at least ALT is recommended as a screening parameter in basic care.


Assuntos
Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Fígado Gorduroso/sangue , Obesidade/sangue , Adolescente , Áustria/epidemiologia , Índice de Massa Corporal , Criança , Pré-Escolar , Fígado Gorduroso/enzimologia , Fígado Gorduroso/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Lactente , Masculino , Obesidade/enzimologia , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Distribuição por Sexo , Suíça/epidemiologia , População Branca
16.
Horm Res Paediatr ; 73(3): 198-204, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20197673

RESUMO

BACKGROUND: P450c17 has two distinct activities: 17alpha-hydroxylase activity and 17,20-lyase activity. Combined 17alpha-hydroxylase/17,20-lyase deficiency leads to a severe defect in the production of cortisol and sex steroids. In affected males this results in impaired masculinization with ambiguous or female external genitalia. Female patients have normal genitalia but show a lack of pubertal development in adolescence. An increased production of mineralocorticoids often leads to hypertension and hypokalemia in both sexes. METHODS: To better understand the mechanisms of P450c17 deficiency, we studied 2 patients (both 46,XY) with combined 17alpha-hydroxylase/17,20-lyase deficiency of different severity: one with complete lack of masculinization and one with ambiguous genitalia. RESULTS: Four mutations were identified by sequencing of the CYP17A1 gene: I332T and A355T in the less severely affected patient; G111S and R440H in the patient with complete lack of masculinization. The three novel mutations were expressed in COS1 cells and all mutant proteins except I332T showed a complete loss of both enzymatic activities. I332T retained some residual 17alpha-hydroxylase as well as 17,20-lyase activity. CONCLUSION: We identified 2 patients with the phenotypical spectrum of P450c17 deficiency. Three novel mutations in the CYP17A1 gene were identified and their functional characterization provided a good phenotype-genotype correlation. The location of the mutated residues in the three-dimensional model of P450c17 gave some additional insights into its structure-function relationship.


Assuntos
Hiperplasia Suprarrenal Congênita/genética , Disgenesia Gonadal 46 XY/genética , Esteroide 17-alfa-Hidroxilase/genética , Animais , Células COS , Chlorocebus aethiops , Feminino , Estudos de Associação Genética , Humanos , Lactente , Masculino , Mutação , Esteroide 17-alfa-Hidroxilase/metabolismo
17.
Acta Paediatr ; 99(4): 569-74, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20050829

RESUMO

AIM: An impressive discrepancy between reported and measured parental height is often observed. The aims of this study were: (a) to assess whether there is a significant difference between the reported and measured parental height; (b) to focus on the reported and, thereafter, measured height of the partner; (c) to analyse its impact on the calculated target height range. METHODS/RESULTS: A total of 1542 individual parents were enrolled. The parents were subdivided into three groups: normal height (3-97th Centile), short (<3%) and tall (>97%) stature. Overall, compared with men, women were far better in estimating their own height (p < 0.001). Where both partners were of normal, short or tall stature, the estimated heights of their partner were quite accurate. Women of normal stature underestimated the short partner and overestimated the tall partner, whereas male partners of normal stature overestimated both their short as well as tall partners. Women of tall stature estimated the heights of their short partners correctly, whereas heights of normal statured men were underestimated. On the other hand, tall men overestimated the heights of their female partners who are of normal and short stature. Furthermore, women of short stature estimated the partners of normal stature adequately, and the heights of their tall partners were overestimated. Interestingly, the short men significantly underestimated the normal, but overestimated tall female partners. CONCLUSION: Only measured heights should be used to perform accurate evaluations of height, particularly when diagnostic tests or treatment interventions are contemplated. For clinical trails, we suggest that only quality measured parental heights are acceptable, as the errors incurred in estimates may enhance/conceal true treatment effects.


Assuntos
Antropometria/métodos , Estatura , Desenvolvimento Infantil , Autoimagem , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Variações Dependentes do Observador , Pais , Fatores Sexuais
18.
Proc Natl Acad Sci U S A ; 106(39): 16574-9, 2009 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-19720994

RESUMO

The challenges corals and symbiotic cnidarians face from global environmental change brings new urgency to understanding fundamental elements of their physiology. Intracellular pH (pHi) influences almost all aspects of cellular physiology but has never been described in anthozoans or symbiotic cnidarians, despite its pivotal role in carbon concentration for photosynthesis and calcification. Using confocal microscopy and the pH sensitive probe carboxy SNARF-1, we mapped pHi in short-term light and dark-incubated cells of the reef coral Stylophora pistillata and the symbiotic anemone Anemonia viridis. In all cells isolated from both species, pHi was markedly lower than the surrounding seawater pH of 8.1. In cells that contained symbiotic algae, mean values of pHi were significantly higher in light treated cells than dark treated cells (7.41 +/- 0.22 versus 7.13 +/- 0.24 for S. pistillata; and 7.29 +/- 0.15 versus 7.01 +/- 0.27 for A. viridis). In contrast, there was no significant difference in pHi in light and dark treated cells without algal symbionts. Close inspection of the interface between host cytoplasm and algal symbionts revealed a distinct area of lower pH adjacent to the symbionts in both light and dark treated cells, possibly associated with the symbiosome membrane complex. These findings are significant developments for the elucidation of models of inorganic carbon transport for photosynthesis and calcification and also provide a cell imaging procedure for future investigations into how pHi and other fundamental intracellular parameters in corals respond to changes in the external environment such as reductions in seawater pH.


Assuntos
Antozoários/fisiologia , Anêmonas-do-Mar/fisiologia , Simbiose , Animais , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Transmissão
19.
Int J Obes (Lond) ; 32(10): 1513-20, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18679408

RESUMO

BACKGROUND: In adults, circulating aP2 may link obesity, inflammation and the metabolic syndrome, but there are few data in children. Experimental models support that dietary factors, particularly dietary fat, may be major determinants of phenotype. OBJECTIVE: The aim of this study was to investigate, in normal, overweight and obese children, the relationships among aP2, the metabolic syndrome, inflammation and diet. DESIGN: This was a cross-sectional study conducted in Northern Switzerland. SUBJECTS: Subjects for this study were 6- to 14-year-old, prepubertal and early pubertal, normal weight, overweight and obese children (n=124). MAIN OUTCOME MEASURES: Body mass index (BMI), body fat percent, waist-to-hip ratio, blood pressure, circulating aP2, fasting insulin, C-reactive protein (CRP), plasma lipids and dietary intakes of macro- and micronutrients were determined. RESULTS: Circulating aP2 markedly increased with increasing central and total adiposity, and predicted measures of insulin resistance. Independent of BMI standard deviation scores and puberty, aP2 correlated with intake of the antioxidant vitamins A, C and E as well as circulating concentrations of CRP, leptin and low-density lipoprotein cholesterol. Children with lower aP2 concentrations consuming high-fat diets did not show an increase in fasting insulin or CRP, whereas those with higher aP2 concentrations showed marked increases in these measures with high intakes of fat or saturated fat. CONCLUSIONS: Increased central and overall adiposity in children are associated with higher circulating aP2 concentrations. In children with high dietary intakes of total fat and saturated fat, but not those with low intakes, higher aP2 concentrations are associated with measures of insulin resistance and inflammation.


Assuntos
Gorduras na Dieta/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Inflamação/metabolismo , Sobrepeso/metabolismo , Adolescente , Índice de Massa Corporal , Criança , Estudos Transversais , Ingestão de Energia/fisiologia , Humanos , Obesidade/metabolismo , Relação Cintura-Quadril
20.
Rev Med Suisse ; 4(146): 533-6, 2008 Feb 27.
Artigo em Francês | MEDLINE | ID: mdl-18402406

RESUMO

The prevalence of childhood obesity increases dramatically. First signs of cardiovascular diseases and type 2 diabetes appear early in life. The treatment of childhood obesity aims at weight maintenance during growth, normalization of body mass index at long-term and prevention of complications. The family based behavioural therapy is a promising approach. It provides simultaneous treatment for the overweight parent and child in order to modify the family environment, to provide role models and support for child behaviour changes. However, this requires group leaders and multiple counselors to meet with families. The treatment should be initiated as soon as possible, as its efficacy is reduced after the onset of puberty. Early preventive interventions that aim to modify both individual's behaviours and the environment are needed.


Assuntos
Obesidade/prevenção & controle , Prevenção Primária , Adolescente , Terapia Comportamental , Índice de Massa Corporal , Peso Corporal , Criança , Comportamento Infantil , Aconselhamento , Relações Familiares , Humanos , Atividade Motora/fisiologia , Relações Pais-Filho , Equipe de Assistência ao Paciente , Puberdade , Meio Social , Resultado do Tratamento
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