Aims/hypothesis Cardiotrophin 1 (CT-1) is a recently described cytokine originally isolated from the heart where it has been shown to play an important role in apoptotic protection of cardiomyocytes and heart hypertrophy. Its beneficial properties have also been described in other organs such as liver and neuromuscular tissue. In the present study, we investigated whether CT-1 can confer protection against pro-apoptotic stimuli in pancreatic beta cells, and its role in insulin secretion and diabetes development.Methods The effects of CT-1 on apoptosis and function were studied using MIN6B1 cells and freshly isolated murine pancreatic islets. The impact on the development of diabetes was evaluated in Ct1-null (Ct1 −/− ) mice (the gene Ct1 is also known as Ctf1) using two streptozotocin (STZ)-induced models of diabetes. Results CT-1 has a protective effect in MIN6B1 cells and murine islets under the pro-apoptotic stimulus of serum deprivation, which correlates with the expression of B cell lymphoma-extra large, or following exposure to a mixture of cytokines. In addition, CT-1 enhances glucose-stimulated insulin secretion in MIN6B1 cells and this was repressed by inhibitors of phospholipase C. Furthermore, Ct1 −/− mice were more prone to develop diabetes, and their glucose tolerance test showed impaired plasma glucose clearance which correlated with decreased pancreatic insulin secretion. Conclusions/interpretation The results obtained from both in vitro and in vivo experiments show that CT-1 improves beta cell function and survival, and protects mice against STZ-induced diabetes.
Objective: To evaluate the recommendations on the most adequate screening method (universal or selective) for thyroid dysfunction. Although thyroid dysfunction is a common disorder in fertile women and untreated cases may have negative maternal, fetal and neonatal outcomes, its screening in preconception and early pregnancy is controversial.
Materials and methods: An evidence-based review was conducted to identify publications since 2017 of American Thyroid Association (ATA) guidelines, according to the following Population, Intervention, Comparison, Outcomes and Study (PICOS): women in preconception or pregnancy without thyroid disease who underwent universal or selective screening for thyroid dysfunction. Study selection obeyed the PRISMA criteria.
Results: We included 15 of 325 publications. The 2017 ATA guidelines recommend selective screening in both preconception and pregnancy. The only two reviews on preconception recommended universal screening. For pregnancy, nine articles suggested universal screening, while a prospective study advocated selective screening. The main benefits advocated for universal screening were easy and low-cost tests; absence of missed diagnosis; safe and inexpensive treatment and its potential in preventing negative outcomes. Iodine deficiency is a decisive indication, but it was not evaluated in all clinical studies. Screening harms and knowledge gaps were the main arguments against universal screening. There are very few cost-effectiveness studies.
Conclusion: We recommend universal screening for thyroid dysfunction in early pregnancy, which is a distinct point of view from 2017 ATA guidelines (weak recommendation, low-quality evidence). It is not possible to make a formal recommendation for preconception (insufficient evidence). We strongly suggest an individualized analysis by each country.
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