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BACKGROUND/OBJECTIVES: To investigate (1) the association of four VDR polymorphisms (TaqI/rs731236, ApaI/rs7975232, FokI/rs10735810, and Bsml/rs1544410) with markers of adiposity and tissue-specific insulin resistance at baseline, after weight loss and weight maintenance; (2) the effect of the VDR polymorphisms in the SAT transcriptome in overweight/obese Caucasians of the DiOGenes cohort. METHODS: We included 553 adult obese individuals (mean BMI 34.8 kg/m2), men (n = 197) and women (n = 356) at baseline, following an 8-week weight loss intervention and 26 weeks weight maintenance. Genotyping was performed using an Illumina 660W-Quad SNP chip on the Illumina iScan Genotyping System. Tissue-specific IR was determined using Hepatic Insulin Resistance Index (HIRI), Muscle Insulin Sensitivity Index (MISI), and Adipose Tissue Insulin Resistance Index (Adipo-IR). Expression quantitative trait loci (eQTL) analysis was performed to determine the effect of SNPs on SAT gene expression. RESULTS: None of the VDR polymorphisms were associated with HIRI or MISI. Interestingly, carriers of the G allele of VDR FokI showed higher Adipo-IR (GG + GA 7.8 ± 0.4 vs. AA 5.6 ± 0.5, P = 0.010) and higher systemic FFA (GG + GA: 637.8 ± 13.4 vs. AA: 547.9 ± 24.7 µmol/L, P = 0.011), even after adjustment with age, sex, center, and FM. However, eQTL analysis showed minor to no effect of these genotypes on the transcriptional level in SAT. Also, VDR polymorphisms were not related to changes in body weight and IR as result of dietary intervention (P > 0.05 for all parameters). CONCLUSIONS: The VDR Fokl variant is associated with elevated circulating FFA and Adipo-IR at baseline. Nevertheless, minor to no effect of VDR SNPs on the transcriptional level in SAT, indicating that putative mechanisms of action remain to be determined. Finally, VDR SNPs did not affect dietary intervention outcome in the present cohort.
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Resistência à Insulina/genética , Obesidade/genética , Receptores de Calcitriol/genética , Adulto , Alelos , Composição Corporal , Feminino , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Ensaios Clínicos Controlados Aleatórios como Assunto , Transcriptoma , População BrancaRESUMO
The association between fish consumption and decreased risk of CVD is well documented. However, studies on health effects of fish consumption suggest that other components than n-3 PUFA have beneficial cardiometabolic effects, including effects on glucose metabolism. The aim of the present study was to investigate effects of salmon fish protein on cardiometabolic risk markers in a double-blind, randomised controlled parallel trial. We hypothesised that daily intake of a salmon fish protein supplement for 8 weeks would improve glucose tolerance in persons with increased risk of type 2 diabetes mellitus (T2DM). Our primary outcome measure was serum glucose (s-glucose) 2 h after a standardised oral glucose tolerance test. In total, eighty-eight adults with elevated s-glucose levels were randomised to 7·5 g of salmon fish protein/d or placebo, and seventy-four participants were included in the analysis. We found no significant effect of salmon fish protein supplementation on our primary outcome or other markers related to glucose tolerance, serum lipids, weight or blood pressure compared with placebo. The present study does not support the hypothesis that daily intake of a salmon fish protein supplement for 8 weeks improves glucose tolerance in persons with increased risk of T2DM.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Suplementos Nutricionais , Proteínas de Peixes/administração & dosagem , Adulto , Animais , Glicemia , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , SalmãoRESUMO
On the basis of the abundance of specific bacterial genera, the human gut microbiota can be divided into two relatively stable groups that might have a role in personalized nutrition. We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets. A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/whole grain or an Average Danish Diet for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models. Among individuals with high P/B the NND resulted in a 3.15 kg (95% confidence interval (CI): 1.55; 4.76, P<0.001) larger body fat loss compared with ADD, whereas no differences was observed among individuals with low P/B (0.88 kg (95% CI: -0.61; 2.37, P=0.25)). Consequently, a 2.27 kg (95% CI: 0.09; 4.45, P=0.041) difference in responsiveness to the diets were found between the two groups. In summary, subjects with high P/B ratio appeared more susceptible to lose body fat on diets high in fiber and whole grain than subjects with a low P/B ratio.
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Bacteroides/fisiologia , Microbioma Gastrointestinal/fisiologia , Sobrepeso/dietoterapia , Prevotella/fisiologia , Redução de Peso/fisiologia , Adulto , Distribuição de Qui-Quadrado , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Resultado do Tratamento , Circunferência da CinturaRESUMO
This corrects the article DOI: 10.1038/ijo.2017.220.
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Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.
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Adiposidade/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Comportamento Sedentário , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Exercício Físico/fisiologia , Finlândia/epidemiologia , Humanos , Obesidade/epidemiologia , Obesidade/genéticaRESUMO
Although the putative therapeutic options for patients with systemic lupus erythematosus (SLE) are steadily increasing, refractory disease is indeed a major challenge to many clinicians and patients. The proteasome inhibitor bortezomib - approved for the treatment of multiple myeloma since the beginning of this century - was recently reported successful in twelve cases of refractory SLE by German colleagues. Herein, we describe two Swedish SLE cases with refractory renal and pulmonary manifestations that were rescued by bortezomib as induction of remission followed by monthly doses of belimumab. The patients were carefully monitored with regard to disease activity and renal function. Anti-dsDNA and anti-C1q antibodies, complement proteins and lymphocyte subsets were analysed in consecutive samples. In December 2016, the patients had been in clinical remission post bortezomib administration for a period of 28 and 22 months, respectively. Potential benefits of using belimumab as maintenance therapy to prevent regeneration of autoreactive B cell clones are discussed.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Bortezomib/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Bortezomib/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/fisiopatologia , Pessoa de Meia-Idade , Inibidores de Proteassoma/administração & dosagem , Inibidores de Proteassoma/uso terapêutico , Suécia , Resultado do TratamentoRESUMO
Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother-infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother-infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (P sex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.
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Desenvolvimento Infantil , Suplementos Nutricionais/efeitos adversos , Óleos de Peixe/efeitos adversos , Transtornos do Crescimento/etiologia , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Pré-Hipertensão/etiologia , Adolescente , Desenvolvimento do Adolescente , Adulto , Estatura , Criança , Dinamarca/epidemiologia , Método Duplo-Cego , Exercício Físico , Feminino , Seguimentos , Transtornos do Crescimento/epidemiologia , Humanos , Masculino , Pré-Hipertensão/epidemiologia , Puberdade Tardia/epidemiologia , Puberdade Tardia/etiologia , Risco , Alimentos Marinhos , Fatores SexuaisRESUMO
Produced water is the main discharge stream from oil and gas production. For offshore activities this water is usually discharged to the marine environment. Produced water contains traces of hydrocarbons such as polycyclic aromatic hydrocarbons as well as alkylphenols, which are relatively resistant to biodegradation and have been reported to cause adverse effects to marine organisms in laboratory studies. For management of produced water, risk-based tools have been developed using toxicity data for mainly non-Arctic species. Reliable risk assessment approaches for Arctic environments are requested to manage potential impacts of produced water associated with increased oil and gas activities in Arctic regions. In order to assess the applicability of existing risk tools for Arctic areas, basic knowledge on the sensitivity of Arctic species has to be developed. In the present study, acute and chronic toxicity of artificial produced water for 6 Arctic and 6 temperate species was experimentally tested and evaluated. The hazardous concentrations affecting 5% and 50% of the species were calculated from species sensitivity distribution curves. Hazardous concentrations were compared to elucidate whether temperate toxicity data used in risk assessment are sufficiently representative for Arctic species. From the study it can be concluded that hazardous concentration derived from individual species' toxicity data of temperate and Arctic species are comparable. However, the manner in which Arctic and non-Arctic populations and communities respond to exposure levels above established thresholds remains to be investigated. Hence, responses at higher levels of biological organization should be studied to reveal potential differences in sensitivities to produced water between Arctic and non-Arctic ecosystems.
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Clima Frio , Peixes , Invertebrados , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Águas Residuárias/toxicidade , Animais , Regiões Árticas , Copépodes , Crangonidae , Crassostrea , Diatomáceas , Ecossistema , Meio Ambiente , Linguados , Gadiformes , Mytilus edulis , Perciformes , Poluição por Petróleo , Fenóis/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Medição de Risco , ÁguaRESUMO
OBJECTIVE: To examine independent and combined cross-sectional associations between movement behaviors (physical activity (PA), sedentary time, sleep duration, screen time and sleep disturbance) and fat mass index (FMI), as well as to examine longitudinal associations between movement behaviors and FMI. METHODS: Cross-sectional and longitudinal analyses were done using data from the OPUS school meal study on 785 children (52% boys, 13.4% overweight, ages 8-11 years). Total PA, moderate-to-vigorous PA (MVPA), sedentary time and sleep duration (7 days and 8 nights) were assessed by an accelerometer and FMI was determined by dual-energy X-ray absorptiometry (DXA) on three occasions over 200 days. Demographic characteristics, screen time and sleep disturbance (Children's Sleep Habits Questionnaire) were also obtained. RESULTS: Total PA, MVPA and sleep duration were negatively associated with FMI, while sedentary time and sleep disturbances were positively associated with FMI (P⩽0.01). However, only total PA, MVPA and sleep duration were independently associated with FMI after adjustment for multiple covariates (P<0.001). Nevertheless, combined associations revealed synergistic effects among the different movement behaviors. Changes over time in MVPA were negatively associated with changes in FMI (P<0.001). However, none of the movement behaviors at baseline predicted changes in FMI (P>0.05), but higher FMI at baseline predicted a decrease in total PA and MVPA, and an increase in sedentary time (P⩽0.001), even in normal-weight children (P⩽0.03). CONCLUSION: Total PA, MVPA and sleep duration were independently associated with FMI, and combined associations of movement behaviors showed a synergistic effect with FMI. In the longitudinal study design, a high FMI at baseline was associated with lower PA and higher sedentary time after 200 days but not vice versa, even in normal-weight children. Our results suggest that adiposity is a better predictor of PA and sedentary behavior changes than the other way around.
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Adiposidade , Dieta , Exercício Físico , Obesidade Infantil/prevenção & controle , Comportamento de Redução do Risco , Sono , Absorciometria de Fóton , Índice de Massa Corporal , Criança , Estudos Transversais , Dinamarca/epidemiologia , Feminino , Humanos , Atividades de Lazer , Estudos Longitudinais , Masculino , Obesidade Infantil/epidemiologia , Aptidão Física , Inquéritos e Questionários , TelevisãoRESUMO
BACKGROUND: Lack of sleep and increased consumption of energy-dense foods and sugar-sweetened beverages (SSBs) have all been suggested as factors contributing to the increased prevalence of overweight and obesity. OBJECTIVE: To evaluate whether objectively measured sleep duration (average and day-to-day variability) as well as parent-reported sleep problems are independently associated with proposed dietary risk factors for overweight and obesity in 8-11-year-old children. DESIGN: In this cross-sectional study, data on sleep duration and day-to-day variability in sleep duration were measured in 676 Danish, apparently healthy children by an objective measure (actigraphy) for 8 nights, and the Children's Sleep Habits Questionnaire (CSHQ) was filled out by the parents. Diet was recorded using a web-based food record for 7 consecutive days. Fasting blood samples were obtained for measurements of plasma leptin and ghrelin levels. RESULTS: Sleep duration (h per night) was negatively associated with energy density (ED) of the diet (ß = -0.32 kJ g(-1)), added sugar (ß = -1.50 E%) and SSBs (ß = -1.07 E%) (all P ≤ 0.003). Furthermore, variability in sleep duration (10-min per night) was positively associated with SSBs (ß = 0.20 E%, P = 0.03), independent of sleep duration, and CSHQ score was positively associated with ED (ß = 0.16 kJ g(-1), P = 0.04). All of these associations were independent of potential confounders (age, sex, pubertal status, height, weight, screen time, moderate-to-vigorous physical activity and parental education and ethnicity). CONCLUSION: Our study suggests that short sleep duration, high sleep duration variability and experiencing sleep problems are all associated with a poor, obesity-promoting diet in children.
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Dieta/efeitos adversos , Comportamento Alimentar , Grelina/sangue , Leptina/sangue , Obesidade Infantil/etiologia , Transtornos do Sono do Ritmo Circadiano/complicações , Análise de Variância , Bebidas/efeitos adversos , Glicemia/metabolismo , Criança , Estudos Transversais , Dinamarca , Carboidratos da Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Sacarose Alimentar/efeitos adversos , Ingestão de Energia , Jejum/sangue , Feminino , Humanos , Pais , Obesidade Infantil/sangue , Obesidade Infantil/prevenção & controle , Prevalência , Fatores de Risco , Transtornos do Sono do Ritmo Circadiano/sangue , Transtornos do Sono do Ritmo Circadiano/prevenção & controle , Inquéritos e QuestionáriosRESUMO
Solid-liquid separation with flocculation can be used as pre-treatment for reverse osmosis (RO) filtration as it produces a liquid fraction (LF) low in suspended solids (SS). However, residual polymers in the LF may foul the membrane. Membrane fouling during RO filtration of swine wastewater containing polymers was investigated with respect to polymer charge density (CD), effluent SS concentration and membrane surface charge. Effluents with 765 mg/L SS and without SS were spiked with low and medium CD polymers (0-40 mg/L effluent) then processed with RO membranes having low and high negative surface charges. Fouling intensity was evaluated by comparing permeate flux and water flux recovery of fouled and cleaned membranes. For effluents containing SS, the presence of polymer reduced permeate flux by 4-16% and water flux recovery of the fouled membrane by 0-18%, relative to effluents without polymer. The extent of the fouling was higher with the low than the medium CD polymer. The fouling was mostly reversible as cleaning allowed for over 95% flux recovery, but the membrane with high negative surface charge was more susceptible to irreversible fouling. Adding the low CD polymer to feed without SS had no effect on permeate flux or flux recovery. Membrane fouling thus appeared to be caused by the polymer changing SS-membrane interaction. If flocculation is applied to pre-treat manure, a medium CD polymer should be used to optimize SS removal and a membrane with low surface charge should be selected to minimize fouling.
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Incrustação Biológica , Membranas Artificiais , Polímeros , Águas Residuárias , Animais , Filtração , Suínos , Gerenciamento de ResíduosRESUMO
Glutamic acid decarboxylase (GAD)(65) formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. In addition, GAD-alum treated patients increased CD4(+) CD25(hi) forkhead box protein 3(+) (FoxP3(+)) cell numbers in response to in-vitro GAD(65) stimulation. We have carried out a 4-year follow-up study of 59 of the original 70 patients to investigate long-term effects on the frequency and function of regulatory T cells after GAD-alum treatment. Peripheral blood mononuclear cells were stimulated in vitro with GAD65 for 7 days and expression of regulatory T cell markers was measured by flow cytometry. Regulatory T cells (CD4(+) CD25(hi) CD127(lo)) and effector T cells (CD4(+) CD25(-) CD127(+)) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. GAD-alum-treated patients displayed higher frequencies of in-vitro GAD(65) -induced CD4(+) CD25(+) CD127(+) as well as CD4(+) CD25(hi) CD127(lo) and CD4(+) FoxP3(+) cells compared to placebo. Moreover, GAD(65) stimulation induced a population of CD4(hi) cells consisting mainly of CD25(+) CD127(+) , which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). Assessment of suppressive function in expanded regulatory T cells revealed no difference between GAD-alum- and placebo-treated individuals. Regulatory T cell frequency did not correlate with C-peptide secretion throughout the study. In conclusion, GAD-alum treatment induced both GAD(65) -reactive CD25(+) CD127(+) and CD25(hi) CD127(lo) cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment.
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Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/terapia , Glutamato Descarboxilase/administração & dosagem , Linfócitos T Reguladores/enzimologia , Linfócitos T Reguladores/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Compostos de Alúmen/administração & dosagem , Autoantígenos/administração & dosagem , Criança , Diabetes Mellitus Tipo 1/enzimologia , Feminino , Seguimentos , Glutamato Descarboxilase/imunologia , Humanos , Terapia de Imunossupressão , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Subunidade alfa de Receptor de Interleucina-7/metabolismo , Ativação Linfocitária , Masculino , Subpopulações de Linfócitos T/enzimologia , Subpopulações de Linfócitos T/imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on chemokines and their receptors. METHODS: Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. RESULTS: Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. CONCLUSION: Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity.
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Hidróxido de Alumínio/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glutamato Descarboxilase/uso terapêutico , Linfócitos T Citotóxicos/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Adolescente , Hidróxido de Alumínio/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Feminino , Citometria de Fluxo , Glutamato Descarboxilase/farmacologia , Humanos , Memória Imunológica , Ativação Linfocitária/efeitos dos fármacos , Masculino , Fenótipo , Receptores CCR4/efeitos dos fármacos , Receptores CCR5/efeitos dos fármacos , SuéciaRESUMO
The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate the role of intracellular complement in isolated, retrogradely buffer-perfused hearts and cardiac cells from adult male wild type mice (WT) and from adult male mice with knockout of complement component 3 (C3KO). Main findings: (i) Intracellular C3 protein was expressed in isolated cardiomyocytes and in whole hearts, (ii) after ischemia-reperfusion injury, C3KO hearts had larger infarct size (32 ± 9% in C3KO vs. 22 ± 7% in WT; p=0.008) and impaired post-ischemic relaxation compared to WT hearts, (iii) C3KO cardiomyocytes had lower basal oxidative respiration compared to WT cardiomyocytes, (iv) blocking mTOR decreased Akt phosphorylation in WT, but not in C3KO cardiomyocytes, (v) after ischemia, WT hearts had higher levels of ATP, but lower levels of both reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+, respectively) compared to C3KO hearts. Conclusion: intracellular C3 protected the heart against ischemia-reperfusion injury, possibly due to its role in metabolic pathways important for energy production and cell survival.
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Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Complemento C3 , Homeostase , Masculino , Camundongos , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismoRESUMO
AIMS/HYPOTHESIS: The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. METHODS: Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 µg of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with <6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. RESULTS: One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 ± 0.032 nmol/l at day 1 and 0.215 ± 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 ± 0.039 and 0.184 ± 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. CONCLUSION/INTERPRETATION: Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. TRIAL REGISTRATION: ClinicalTrials.gov NCT00435981 FUNDING: The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Glutamato Descarboxilase/uso terapêutico , Adolescente , Peptídeo C/metabolismo , Criança , Diabetes Mellitus Tipo 1/metabolismo , Método Duplo-Cego , Feminino , Glutamato Descarboxilase/efeitos adversos , Humanos , Masculino , Resultado do TratamentoRESUMO
Phosphorus (P) in manure is a nutrient source for plants, but surplus P amended to fields represents a risk to the environment. This study examines the interactions between low-P diets for pigs and dairy cows and the separation of animal slurry into a solid P fraction and a liquid fraction. Replacing inorganic phosphates with phytase in pig feed reduced the concentration of P in slurry by 35%, but supplementing concentrates to dairy cows did not affect the P concentration in cattle slurry. Particle-size fractions of the slurry were not affected by these dietary changes. The amount of dry matter (DM) in the < 0.025 mm fraction was greater in pig slurry than in cattle slurry, but the relative amounts of P and nitrogen (N) were larger in the > 0.025 mm fraction. Replacing feed phosphate, in the form of mono-calcium phosphate, with phytase in the pig diet reduced the separation index (efficiency) of P from 80% to 60%.
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Criação de Animais Domésticos/métodos , Bovinos/metabolismo , Fezes/química , Fósforo/metabolismo , Suínos/metabolismo , Animais , Floculação , Nitrogênio/análise , Fósforo/análise , Eliminação de Resíduos/métodosRESUMO
Decades of research have reported only weak associations between the intakes of specific foods or drinks and weight gain and obesity. Randomized controlled dietary intervention trials have only shown very modest effects of changes in nutrient intake and diet composition on body weight in obese subjects. This review summarizes the scientific evidence on the role mental stress (either in or not in association with impaired sleep) may play in poor sleep, enhanced appetite, cravings and decreased motivation for physical activity. All these factors contribute to weight gain and obesity, possibly via decreasing the efficacy of weight loss interventions. We also review evidence for the role that lifestyle and stress management may play in achieving weight loss in stress-vulnerable individuals with overweight.
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Comportamento Alimentar , Obesidade Abdominal/epidemiologia , Sono , Estresse Fisiológico , Aumento de Peso , Redução de Peso , Ansiedade/complicações , Ansiedade/epidemiologia , Apetite , Índice de Massa Corporal , Dieta , Exercício Físico , Humanos , Estilo de Vida , Obesidade Abdominal/terapia , Estudos Observacionais como Assunto , Prevalência , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: Skeletal muscle is an important secretory organ, producing and releasing numerous myokines, which may be involved in mediating beneficial health effects of physical activity. More than 100 myokines have been identified by different proteomics approaches, but these techniques may not detect all myokines. We used mRNA sequencing as an untargeted approach to study gene expression of secreted proteins in skeletal muscle upon acute as well as long-term exercise. METHODS: Twenty-six middle-aged, sedentary men underwent combined endurance and strength training for 12 weeks. Skeletal muscle biopsies from m. vastus lateralis and blood samples were taken before and after an acute bicycle test, performed at baseline as well as after 12 weeks of training intervention. We identified transcripts encoding secretory proteins that were changed more than 1.5-fold in muscle after exercise. Secretory proteins were defined based on either curated UniProt annotations or predictions made by multiple bioinformatics methods. RESULTS: This approach led to the identification of 161 candidate secretory transcripts that were up-regulated after acute exercise and 99 that where increased after 12 weeks exercise training. Furthermore, 92 secretory transcripts were decreased after acute and/or long-term physical activity. From these responsive transcripts, we selected 17 candidate myokines sensitive to short- and/or long-term exercise that have not been described as myokines before. The expression of these transcripts was confirmed in primary human skeletal muscle cells during in vitro differentiation and electrical pulse stimulation (EPS). One of the candidates we identified was macrophage colony-stimulating factor-1 (CSF1), which influences macrophage homeostasis. CSF1 mRNA increased in skeletal muscle after acute and long-term exercise, which was accompanied by a rise in circulating CSF1 protein. In cultured muscle cells, EPS promoted a significant increase in the expression and secretion of CSF1. CONCLUSION: We identified 17 new, exercise-responsive transcripts encoding secretory proteins. We further identified CSF1 as a novel myokine, which is secreted from cultured muscle cells and up-regulated in muscle and plasma after acute exercise.
Assuntos
Exercício Físico , Músculo Esquelético/metabolismo , Hormônios Peptídicos/genética , Transcriptoma , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Hormônios Peptídicos/metabolismoRESUMO
BACKGROUND: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. METHODS: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.
Assuntos
Anticoagulantes/uso terapêutico , Síndrome Pós-Flebítica/etiologia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/mortalidade , Varfarina/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Tromboembolia/diagnóstico , Fatores de Tempo , Trombose Venosa/patologia , Vitamina K/antagonistas & inibidoresRESUMO
This study aimed to investigate functional responses of natural marine planktonic communities to stress from the antifouling compound zinc pyrithione (ZPT). Isotope labelling techniques (14C) were applied to study bacterial incorporation of leucine, photosynthetic activity of phytoplankton and grazing of labelled prey by zooplankton communities for 6 days after exposures to nominal concentrations of 0, 5, 25, 50 nM ZPT in a mesocosm experiment in Isefjord, Denmark. Significant direct effects were visible on chlorophyll a concentrations, which decreased in all exposed communities, to between 48 and 36% of control concentrations on Day 3, 1 day after the last exposure. Phytoplankton activities were also significantly affected on Day 3 with activities between 9 and 26% of control levels, as was zooplankton activities in the 25 and 50 nM exposures. In the 50 nM exposure the total community zooplankton activity was reduced to 25+/-4%, and per individual to 46+/-11% of control levels. Bacterial communities showed positive indirect effects with high activities (up to 183+/-40%) due to higher amounts of available substrate from algal death. Pollution induced community tolerance analyses performed on phytoplankton and bacterial communities at the end of the experiment indicated a development of increased tolerance for phytoplankton in the 50 nM exposed communities, whereas there were no changes in tolerance in the bacterial communities. Multivariate analysis of the integrated functional response by the plankton communities revealed a significant difference (p<0.05) between exposed communities compared to controls in the first 3 days after last exposure and in the end of the experiment. The study provides evidence of diverse effects on the functions of marine plankton communities under stress from a pollutant. Direct effects lead to cascading indirect effects throughout the community, eventually causing different developments. Continuous exposure to ZPT could lead to severe long-term effects, causing more permanent changes in structure and function than observed here. The study demonstrates that it is possible to assess the functional effects of a stressor in a complex mesocosm system, and to determine effects in a complex plankton community, which were not predictable from laboratory studies.