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BACKGROUND: Glucocorticoid sparing in rheumatoid arthritis (RA) treatment is crucial to minimizing adverse effects associated with long-term use. Janus kinase inhibitors (JAKi) could potentially offer a more potent glucocorticoid-sparing effect than biological Disease-Modifying Antirheumatic Drugs (bDMARDs). MATERIAL AND METHODS: This is a single-center retrospective analysis of RA patients treated with JAKi or bDMARDs. Glucocorticoid tapering, rescue therapy and discontinuation were analyzed through mixed-effects models, Poisson regression, and multivariable logistic regression, respectively, adjusting for baseline disease activity, demographic factors, and treatment line. RESULTS: A total of 716 RA patients treated with JAKi (n = 156) or bDMARDs (n = 560) were evaluated. JAKi treatment was associated with a more rapid reduction in glucocorticoid dose within the first 6 months and 60% higher odds of discontinuation compared with bDMARDs (adjusted odds ratio 1.63, 95% CI 1.02-2.60, p 0.039). Despite a higher baseline glucocorticoid dose, over 50% of JAKi-treated patients discontinued glucocorticoids after 12 months, vs â¼40% for bDMARDs. The need for glucocorticoid rescue therapy was significantly higher in the bDMARD group (rate ratio 2.66 (95% CI, 1.88-3.74)). CONCLUSION: Our findings indicate that JAK inhibitors facilitate more rapid glucocorticoid tapering compared with bDMARDs in RA patients. These results underscore the potential of JAK inhibitors to reduce long-term glucocorticoid exposure, highlighting their value in RA management strategies, including minimizing glucocorticoid-related adverse effects.
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Sorghum grain is a staple food for about 500 million people in 30 countries in Africa and Asia. Despite this contribution to global food production, most of the world's sorghum grain, and nearly all in Western countries, is used as animal feed. A combination of the increasingly important ability of sorghum crops to resist heat and drought, the limited history of the use of sorghum in Western foods, and the excellent functional properties of sorghum grain in healthy diets, suggests a greater focus on the development of new sorghum-based foods. An understanding of the structural and functional properties of sorghum grain to develop processes for production of new sorghum-based foods is required. In this review, we discuss the potential of sorghum in new food products, including sorghum grain composition, the functional properties of sorghum in foods, processing of sorghum-based products, the digestibility of sorghum protein and starch compared to other grains, and the health benefits of sorghum. In the potential for sorghum as a major ingredient in new foods, we suggest that the gluten-free status of sorghum is of relatively minor importance compared to the functionality of the slowly digested starch and the health benefits of the phenolic compounds present.
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Sorghum , Animais , Sorghum/química , Grão Comestível/química , Amido/química , Ração Animal/análise , ÁfricaRESUMO
BACKGROUND: The innate immune response against various life cycle stages of the malaria parasite plays an important role in protection against the disease and regulation of its severity. Phagocytosis of asexual erythrocytic stages is well documented, but little and contrasting results are available about phagocytic clearance of sexual stages, the gametocytes, which are responsible for the transmission of the parasites from humans to mosquitoes. Similarly, activation of host macrophages by gametocytes has not yet been carefully addressed. METHODS: Phagocytosis of early or late Plasmodium falciparum gametocytes was evaluated through methanol fixed cytospin preparations of immortalized mouse C57Bl/6 bone marrow-derived macrophages treated for 2 h with P. falciparum and stained with Giemsa, and it was confirmed through a standardized bioluminescent method using the transgenic P. falciparum 3D7elo1-pfs16-CBG99 strain. Activation was evaluated by measuring nitric oxide or cytokine levels in the supernatants of immortalized mouse C57Bl/6 bone marrow-derived macrophages treated with early or late gametocytes. RESULTS: The results showed that murine bone marrow-derived macrophages can phagocytose both early and late gametocytes, but only the latter were able to induce the production of inflammatory mediators, specifically nitric oxide and the cytokines tumour necrosis factor and macrophage inflammatory protein 2. CONCLUSIONS: These results support the hypothesis that developing gametocytes interact in different ways with innate immune cells of the host. Moreover, the present study proposes that early and late gametocytes act differently as targets for innate immune responses.
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Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Fagocitose/imunologia , Plasmodium falciparum/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Prenatal dexamethasone (DEX) treatment in congenital adrenal hyperplasia (CAH) is effective in reducing virilization in affected girls, but potential long-term adverse effects are largely unknown. In this report we intended to explore potential side effects of DEX therapy to enhance the adequacy of future risk benefit analyses of DEX treatment. We investigated the long-term effects of first trimester prenatal DEX treatment on behavioral problems and temperament in children and adolescents aged 7-17â¯years. The study included 34 children and adolescents, without CAH, who had been exposed to DEX during the first trimester and 67 untreated controls. Standardized parent-completed questionnaires were used to evaluate adaptive functioning and behavioral/emotional problems (CBCL), social anxiety (SPAI-C-P), and temperament (EAS) in the child. Self-reports were used to assess the children's perception of social anxiety (SASC-R). No statistically significant differences were found between DEX-treated and control children and adolescents, suggesting that, in general, healthy children treated with DEX during early fetal life are well adjusted.
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Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Dexametasona/uso terapêutico , Feto/efeitos dos fármacos , Cuidado Pré-Natal/métodos , Comportamento Problema , Virilismo/prevenção & controle , Adolescente , Hiperplasia Suprarrenal Congênita/psicologia , Estudos de Casos e Controles , Criança , Emoções/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Fatores de Risco , Suécia , Temperamento/efeitos dos fármacos , Resultado do TratamentoRESUMO
Meat and meat products constitute important source of protein, fat, and several functional compounds. Although beef consumption may implicate possible negative impacts on human health, its consumption can also contribute to human health. Quality traits of beef, as well as its nutritional properties, depend on animal genetics, feeding, livestock practices, and post mortem procedures. Available data show that emerging beef production systems are able to improve both, quality and nutritional traits of beef in a sustainable way. In this context, Argentina's actions are aimed at maximising beef beneficial effects and minimising its negative impact on human health, in a way of contributing to global food security.
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Criação de Animais Domésticos/métodos , Saúde , Carne/análise , Animais , Argentina , Bovinos , Humanos , Lipídeos/análise , Carne/economia , Carne/normas , Proteínas/análiseRESUMO
Aquifer contamination with diesel fuel is a worldwide environmental problem, and related available remediation technologies may not be adequately efficient, especially for the simultaneous treatment of both solid and water phases. In this paper, a lab-scale 2.45 GHz microwave (MW) treatment of an artificially diesel-contaminated aquifer was applied to investigate the effects of operating power (160, 350 and 500 W) and time on temperature profiles and contaminant removal from both solid and water phases. Results suggest that in diesel-contaminated aquifer MW remediation, power significantly influences the final reachable temperature and, consequently, contaminant removal kinetics. A maximum temperature of about 120 °C was reached at 500 W. Observed temperature values depended on the simultaneous irradiation of both aquifer grains and groundwater. In this case, solid phase heating is limited by the maximum temperature that interstitial water can reach before evaporation. A minimal residual diesel concentration of about 100 mg kg(-1) or 100 mg L(-1) was achieved by applying a power of 500 W for a time of 60 min for the solid or water phase, respectively. Measured residual TPH fractions showed that MW heating resulted in preferential effects of the removal of different TPH molecular weight fractions and that the evaporation-stripping phenomena plays a major role in final contaminant removal processes. The power low kinetic equation shows an excellent fit (r(2) > 0.993) with the solid phase residual concentration observed for all the powers investigated. A maximum diesel removal of 88 or 80% was observed for the MW treatment of the solid or water phase, respectively, highlighting the possibility to successfully and simultaneously remediate both the aquifer phases. Consequently, MW, compared to other biological or chemical-physical treatments, appears to be a better choice for the fast remediation of diesel-contaminated aquifers.
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Recuperação e Remediação Ambiental/métodos , Gasolina , Micro-Ondas , Poluentes Químicos da Água , Água Subterrânea/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificaçãoRESUMO
Triticale (×Triticosecale) is a hybrid between wheat (Triticum spp.) and rye (Secale cereale), producing higher grain yields than wheat in challenging environments. Triticale grain is also highly nutritious. Thus, the potential of triticale grain for an expanded range of food applications should be explored. Sourdough bread has unique functional and nutritional properties, but understanding the effects of partial substitution of triticale for wheat flour and varying levels of dough moisture content on sourdough quality requires further research. The aim of this study was to evaluate the wholegrain flour of contrasting triticale cultivars in comparison to that of a common wheat cultivar in commercial sourdough breadmaking. Two triticale cultivars (Goanna and Hawkeye, selected from a panel of Australian genotypes) and one wheat cultivar (Scout) were grown in a field trial in northern NSW, Australia. Differences in quantitative texture and color parameters of the dough and sourdough bread resulting from (1) substitution of commercial wholemeal wheat flour with different proportions of wholegrain triticale or wholegrain wheat (Scout) flour (0%, 60%, 70%, 80%, and 90%) and (2) varying the amount of water included in the dough preparation (70%, 80%, 90%, and 100 g water/100 g flour) were determined. Replacement of wholemeal wheat flour with 60% wholegrain Goanna flour (protein content 12.76%; c.f. 11.50% for Hawkeye, 12.40% for Scout), and addition of 100 g water/100 g flour in the dough preparation gave the highest quality sourdough bread based on specific volume, texture, and color parameters and had similar properties to the control made from wheat alone.
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Sam68 plays an essential role in mouse spermatogenesis and male fertility. Herein, we report an interaction between Sam68 and the phosphorylated forms of the RNA polymerase II (RNAPII) in meiotic spermatocytes. RNase treatment decreased but did not abolish the interaction, consistently with in vitro binding of RNAPII to the Sam68 carboxyl-terminal region. Sam68 retention in the spermatocyte nucleus was dependent on the integrity of cellular RNAs, suggesting that the protein is recruited to transcriptionally active chromatin. Mouse knockout models characterized by stage-specific arrest of spermatogenesis and staining with the phosphorylated form of RNAPII documented that Sam68 expression is confined to the transcriptionally active stages of spermatogenesis. Furthermore, Sam68 associates with splicing regulators in germ cells and we report that alternative splicing of Sgce exon 8 is regulated in a Sam68-dependent manner during spermatogenesis. RNA and chromatin crosslink immunoprecipitation experiments showed that Sam68 binds in vivo to sequences surrounding the intron 7/exon 8 boundary, thereby affecting the recruitment of the phosphorylated RNAPII and of the general splicing factor U2AF65. These results suggest that Sam68 regulates alternative splicing at transcriptionally active sites in differentiating germ cells and provide new insights into the regulation of Sam68 expression during spermatogenesis.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Processamento Alternativo , Proteínas de Ligação a RNA/metabolismo , Espermatogênese/genética , Espermatozoides/metabolismo , Transcrição Gênica , Animais , Masculino , Prófase Meiótica I/genética , Camundongos , Camundongos Knockout , RNA Polimerase II/metabolismo , Sarcoglicanas/genética , Sarcoglicanas/metabolismo , Espermatócitos/enzimologia , Espermatócitos/metabolismoRESUMO
The textural changes during storage of two freeze-dried candies developed from blackcurrant fruits, unflavored yogurt, and different alternative sweeteners, one sweetened with honey/isomalt (HI) and another sweetened with isomalt/stevia (IS), were analyzed using three different methods (instrumental, sensory, and image analysis). Fresh candies were in the supercooled state and presented different structural and textural characteristics (HI: compact and homogeneous, and IS: porous and crunchy), with Fmax values of 139 ± 14 and 174 ± 16 N for HI and IS, respectively. After storage, the instrumental analysis showed approximately 60% average drop in Fmax and W values, in agreement with the decrease observed by sensory analysis in hardness, fracturability, and crispness. Image analysis showed an increase in parameters related to the homogeneity and the uniformity/smoothness for HI. Pearson's correlation coefficients analysis showed that there was a good correlation between the three techniques used, suggesting that the joint use of these methods could be performed for a better understanding of complex food texture.
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Doces , Armazenamento de Alimentos , Frutas , Edulcorantes , MelRESUMO
CONTEXT: Patients with congenital adrenal hyperplasia (CAH) require life-long replacement of cortisol. Problems with cognitive function, especially working memory, have previously been identified, but the long-term effects of this disease on brain function are unknown. OBJECTIVE: We investigate brain activity during working memory in CAH compared to controls. DESIGN, SETTING, AND PARTICIPANTS: Twenty-nine individuals with CAH (17 females) and 40 healthy controls (24 females), 16-33 years, from a single research institute, underwent functional magnetic resonance imaging while doing a verbal and visuospatial working memory task. RESULTS: Individuals with CAH responded faster on the verbal task. Although we found no differences in BOLD response over the whole group, there were significant interactions with sex: CAH males had increased activity in the bilateral lateral superior occipital cortex, left supramarginal and angular gyri, left precuneus, left posterior cingulate cortex and bilateral cerebellum during decoding of the visuospatial task, while females showed decreased activity in these regions. CONCLUSIONS: Long-term cortisol imbalances do not seem to have a major impact on the functional brain responses during working memory in CAH. However, activity of the left dorsal visual stream in particular might be affected depending on sex. As the task employed may have been relatively easy, larger studies using more complex tasks are needed to further investigate this.
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Hiperplasia Suprarrenal Congênita , Memória de Curto Prazo , Masculino , Feminino , Humanos , Memória de Curto Prazo/fisiologia , Hiperplasia Suprarrenal Congênita/psicologia , Hidrocortisona/farmacologia , Encéfalo/fisiologia , Cognição/fisiologia , Imageamento por Ressonância MagnéticaRESUMO
Detecting the trends of species and populations is fundamental to identifying taxa with high conservation priority. Unfortunately, long-term monitoring programs are challenging and often lacking. The Italian agile frog Rana latastei is endemic to Northern Italy and adjacent countries, is considered vulnerable by the IUCN, and is protected at the European level. However, quantitative estimates of its decline are extremely scarce. In this study, we document the trends in abundance and distribution of Rana latastei within Monza Park, which currently represents the area closer to the type locality of the species and holds unique genetic features. Wetlands within the park were monitored from 2000 to 2023; counts of egg clutches were taken as a measure of reproductive output and the abundance of breeding females. In 2000, the species occurred over a significant proportion of the park. Total abundance showed strong yearly variation but remained rather constant from 2000 to 2019. However, Rana latastei disappeared from the park around 2021 and was never detected in 2022-2023. The decline is probably related to the joint effect of multiple factors, including the conversion of breeding sites for farming, inappropriate water management, invasive alien species, and severe drought. The local extinction of Rana latastei occurred despite legal protection, highlighting the need for more effective and stringent tools for the conservation of European biodiversity.
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First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in girls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up research is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DEX may avoid unnecessary treatment and improve treatment safety.
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Introduction: Recent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of P. falciparum malaria by providing a "niche" for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized in vivo models to study the mechanisms of the interplay between the parasite and the human BM components are still missing. Methods: We report a novel experimental system based on the infusion of immature P. falciparum gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells. Results: We demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types. Discussion: Our model represents a powerful tool to study BM function and the interplay essential for parasite transmission in P. falciparum malaria and can be extended to study other infections in which the human BM plays a role.
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Malária Falciparum , Malária , Parasitos , Humanos , Animais , Camundongos , Plasmodium falciparum , Medula Óssea/parasitologia , Malária Falciparum/parasitologiaRESUMO
CONTEXT: Prenatal treatment with dexamethasone (DEX) has been used to prevent virilization in females at risk of congenital adrenal hyperplasia (CAH). Both affected and unaffected girls, as well boys, are treated until the genotype and sex of the fetus is known (gestational weeks 10-12). After that, only affected girls are treated until term. Exposure to a high synthetic glucocorticoid dosage may alter the developmental trajectory of the brain, with alterations in resting-state functional connectivity of the brain at adult age. OBJECTIVE: To investigate resting-state functional connectivity in subjects at risk of having CAH, exposed to DEX treatment during the first trimester of fetal life, both in the whole brain and in 3 regions of interest (amygdala, hippocampus, and superior frontal gyrus). DESIGN, SETTING, AND PARTICIPANTS: Eighteen participants (8 females) at risk of having CAH, exposed to DEX treatment, and 38 controls (24 females), age range 16 to 26 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. We used 2 different approaches: an exploratory whole-brain analysis and seed-based analysis. For seed-based analysis, we chose 3 different brain regions (amygdala, hippocampus, and superior frontal gyrus) based on our previous findings and literature evidence. RESULTS: We did not observe any differences in functional connectivity during rest, either in the whole brain nor in seed-based connectivity analyses at this adolescent and young adult age. CONCLUSIONS: Our results are reassuring; however, future studies on larger samples and with more sensitive methodologies are needed to confirm these findings.
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Hiperplasia Suprarrenal Congênita , Glucocorticoides , Adolescente , Adulto , Dexametasona/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Gravidez , Primeiro Trimestre da Gravidez , Virilismo/prevenção & controle , Adulto JovemRESUMO
CONTEXT: Patients with congenital adrenal hyperplasia (CAH) are treated with life-long glucocorticoid (GC) replacement therapy. Negative effects on cognition, brain structure and function during working memory tasks have been identified. To date, no studies on functional connectivity during rest have been performed in patients with CAH. OBJECTIVE: To investigate resting-state functional connectivity in patients with CAH compared with healthy untreated controls and the association between functional connectivity in the precuneus and disease severity, dose of GC and working memory (WM). DESIGN, SETTING AND PARTICIPANTS: Thirty-one patients with CAH (18 females) and 38 healthy controls (24 females), aged 16-33 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. RESULTS: Patients with CAH showed increased functional connectivity in the precuneus compared with controls. Post-hoc tests within the precuneus showed that only patients with simple virilising CAH had stronger connectivity compared to controls. Further, while both patients with salt-wasting and simple virilising CAH performed worse on a WM task compared to controls, functional connectivity in the precuneus was not associated with executive function performance. CONCLUSION: Patients with CAH demonstrated altered functional connectivity during rest in the precuneus. Such a change may reflect a functional reorganisation in response to the CAH disease. The change in functional connectivity may depend on the severity of CAH.
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Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico por imagem , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Cognição/fisiologia , Função Executiva , Feminino , Glucocorticoides , Humanos , Imageamento por Ressonância Magnética , Memória de Curto Prazo , DescansoRESUMO
To gain access to the intracellular cytoplasmic niche essential for their growth and replication, apicomplexan parasites such as Toxoplasma gondii rely on the timely secretion of two types of apical organelles named micronemes and rhoptries. Rhoptry proteins are key to host cell invasion and remodeling, however, the molecular mechanisms underlying the tight control of rhoptry discharge are poorly understood. Here, we report the identification and functional characterization of two novel T. gondii thrombospondin-related proteins implicated in rhoptry exocytosis. The two proteins, already annotated as MIC15 and MIC14, were renamed rhoptry discharge factor 1 (RDF1) and rhoptry discharge factor 2 (RDF2) and found to be exclusive of the Coccidia class of apicomplexan parasites. Furthermore, they were shown to have a paralogous relationship and share a C-terminal transmembrane domain followed by a short cytoplasmic tail. Immunofluorescence analysis of T. gondii tachyzoites revealed that RDF1 presents a diffuse punctate localization not reminiscent of any know subcellular compartment, whereas RDF2 was not detected. Using a conditional knockdown approach, we demonstrated that RDF1 loss caused a marked growth defect. The lack of the protein did not affect parasite gliding motility, host cell attachment, replication and egress, whereas invasion was dramatically reduced. Notably, while RDF1 depletion did not result in altered microneme exocytosis, rhoptry discharge was found to be heavily impaired. Interestingly, rhoptry secretion was reversed by spontaneous upregulation of the RDF2 gene in knockdown parasites grown under constant RDF1 repression. Collectively, our results identify RDF1 and RDF2 as additional key players in the pathway controlling rhoptry discharge. Furthermore, this study unveils a new example of compensatory mechanism contributing to phenotypic plasticity in T. gondii.
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Translation of stored mRNAs accounts for protein synthesis during the transcriptionally inactive stages of spermatogenesis. A key step in mRNA translation is the assembly of the initiation complex EIF4F, which is regulated by the MTOR (mammalian target of rapamycin) and MNK1/2 (MAP kinase-interacting kinase 1 and 2) pathways. We investigated the expression and activity of regulatory proteins of these pathways in male germ cells at different stages of differentiation. All translation factors analyzed were expressed in germ cells throughout spermatogenesis. However, while EIF4G and PABP1 (poly[A]-binding protein 1) were more abundant in postmeiotic cells, MTOR and its target EIF4EBP1 (4E-BP1) decreased steadily during spermatogenesis. In vivo labeling showed that pachytene spermatocytes display higher rates of protein synthesis, which are partially dependent on MTOR and MNK activity. By contrast, haploid spermatids are characterized by lower levels of protein synthesis, which are independent of the activity of these pathways. Accordingly, MTOR and MNK activity enhanced formation of the EIF4F complex in pachytene spermatocytes but not in round spermatids. Moreover, external cues differentially modulated the activity of these pathways in meiotic and haploid cells. Heat shock decreased MTOR and MNK activity in pachytene spermatocytes, whereas round spermatids were much less sensitive. On the other hand, treatment with the phosphatase inhibitor okadaic acid activated MTOR and MNK in both cell types. These results indicate that translational regulation is differentially dependent on the MTOR and MNK pathways in mouse spermatocytes and spermatids and suggest that the late stages of germ cell differentiation display constitutive assembly of the translation initiation complex.
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Regulação Enzimológica da Expressão Gênica/fisiologia , Meiose/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , Espermatócitos/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Western Blotting , Diferenciação Celular/fisiologia , Inibidores Enzimáticos/farmacologia , Fator de Iniciação 4F em Eucariotos/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Ácido Okadáico/farmacologia , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , Transdução de Sinais , Espermatócitos/citologia , Espermatócitos/metabolismo , Espermatogênese/fisiologiaRESUMO
BACKGROUND: Prenatal treatment with dexamethasone (DEX) reduces virilization in girls with congenital adrenal hyperplasia (CAH). The treatment is effective but may result in long-lasting adverse effects. In this study we explore the effects of DEX on metabolism in individuals not having CAH but treated with DEX during the first trimester of fetal life. METHOD: All DEX-treated participants (nâ =â 40, age range 5.1-26.4 years) and controls (nâ =â 75, age range 4.5-26.6 years) were assessed with fasting blood samples to measure blood count, renal function, glucose homeostasis, and serum lipid profiles. RESULTS: There were no significant differences between DEX and control participants for birth parameters, weight and height, or body mass index at the time of testing. Analyzing the entire cohort, we found no significant effects of DEX on blood count, renal function, or serum lipid profiles. However, a lower HOMA-ß index in the DEX-treated individuals (Uâ =â 893.0; Pâ =â 0.049) was observed. Post hoc analyses revealed an effect in girls (Uâ =â 152.5; Pâ =â 0.024) but not in boys (Uâ =â 299.5; Pâ =â 0.550). The effect on HOMA-ß persisted (Uâ =â 117.5; Pâ =â 0.048) after analyzing data separately in the participants < 16 years of age. In addition, we observed higher plasma glucose levels (F =â 14.6; Pâ =â 0.001) in the DEX-treated group. The participants ≥ 16 years of age in the DEX-treated group had significantly higher total plasma cholesterol (F =â 9.8; Pâ =â 0.003) and higher low-density lipoprotein cholesterol levels (F =â 7.4; Pâ =â 0,009). CONCLUSION: Prenatal DEX exposure in early pregnancy has negative effects on beta-cell function and lipid profile in individuals without CAH already at a young age.
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Hiperplasia Suprarrenal Congênita/prevenção & controle , Dexametasona/efeitos adversos , Células Secretoras de Insulina/metabolismo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Adolescente , Adulto , Glicemia , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Feminino , Testes Hematológicos , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Gravidez , Primeiro Trimestre da Gravidez , Fatores de Risco , Adulto JovemRESUMO
CONTEXT: Patients with classic congenital adrenal hyperplasia (CAH) are treated postnatally with lifelong glucocorticoid (GC) replacement therapy. Previous results on general cognitive ability in individuals with CAH have been conflicting. OBJECTIVE: To evaluate long-term cognitive effects of GC replacement therapy and the impact of early diagnosis in children with CAH. DESIGN AND SETTING: Observational study with patients from a single research institute. PATIENTS: 32 children with CAH (mean age 11.5 years) identified through the Swedish national neonatal screening program for CAH and 52 matched population controls (mean age 10.7 years). Eleven (6 female) children with CAH who were treated prenatally with dexamethasone (DEX), (CAH-DEX) (mean age 11.7 years). INTERVENTION: GC replacement therapy, neonatal screening for CAH. MEASURES: Cognitive abilities assessed with standardized neuropsychological tests (Wechsler scales, Span Board Test, Stroop Interference Test, NEPSY list learning). RESULTS: Children with CAH (not prenatally treated) performed equally well as population controls on a series of tests assessing general intellectual ability and executive functions. No significant differences were observed in cognitive performance between patients with different genotypes (null, non-null). Patients with salt-wasting CAH performed poorer than patients with simple virilizing CAH in a test assessing visuo-spatial working memory (Pâ =â 0.039), although the performance was within the normal range for the population. Prenatally DEX-treated girls with CAH had lower verbal intellectual ability compared with CAH girls not exposed to prenatal treatment (Pâ =â 0.037). CONCLUSION: Children and adolescents with CAH who were diagnosed early via a neonatal screening program and treated with hydrocortisone had normal psychometric intelligence and executive functions.
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Hiperplasia Suprarrenal Congênita/psicologia , Cognição , Adolescente , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/epidemiologia , Estudos de Casos e Controles , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Cognição/fisiologia , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Diagnóstico Precoce , Feminino , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/farmacologia , Recém-Nascido , Estudos Longitudinais , Masculino , Triagem Neonatal , Testes Neuropsicológicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Suécia/epidemiologia , Fatores de TempoRESUMO
CONTEXT: Prenatal dexamethasone (DEX) treatment is sometimes used in pregnancies at risk for congenital adrenal hyperplasia (CAH) to prevent virilization in female fetuses with CAH. In boys and in fetuses not having CAH, there is no benefit of early DEX treatment and the risks of this therapy must be thoroughly investigated. High doses of prenatal glucocorticoid might alter the developmental trajectory of the brain into adulthood, even for CAH unaffected subjects treated with DEX for a short term during the first trimester. OBJECTIVE: The present study investigated brain activation during working memory performance in DEX-treated subjects compared with controls. DESIGN, SETTING, AND PARTICIPANTS: We tested 18 participants who were exposed to DEX during the first trimester of fetal life but did not have CAH (8 females; mean age 20.78 [standard deviation (SD), 2.67] years) and 40 control participants (24 females; mean age 20.53 [SD, 2.64]) from a single research institute. Participants underwent functional magnetic resonance imaging on a 3T scanner during a verbal and visuospatial working memory task. RESULTS: We did not observe any differences in brain activity during working memory performance. However, DEX-treated subjects responded faster during the experimental condition of the verbal WM task. CONCLUSIONS: First trimester DEX treatment did not seem to result in altered working memory-related brain activity at adult age. Our findings contribute to the risk-benefit assessment of prenatal DEX treatment in the context of CAH.