Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms

Background:Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart.Methods:Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.Results:Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells.Conclusions:Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actionsThis work was supported by national funding from Ministerio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/ BIO-5289), and a unrestricted grant from by Merck/MS

Gut Microbiota, Probiotics and Diabetes

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes

Fin-Tail Coordination during Escape and Predatory Behavior in Larval Zebrafish

Larval zebrafish innately perform a suite of behaviors that are tightly linked to their evolutionary past, notably escape from threatening stimuli and pursuit and capture of prey. These behaviors have been carefully examined in the past, but mostly with regard to the movements of the trunk and tail of the larvae. Here, we employ kinematics analyses to describe the movements of the pectoral fins during escape and predatory behavior. In accord with previous studies, we find roles for the pectoral fins in slow swimming and immediately after striking prey. We find novel roles for the pectoral fins in long-latency, but not in short-latency C-bends. We also observe fin movements that occur during orienting J-turns and S-starts that drive high-velocity predatory strikes. Finally, we find that the use of pectoral fins following a predatory strike is scaled to the velocity of the strike, supporting a role for the fins in braking. The implications of these results for central control of coordinated movements are discussed, and we hope that these results will provide baselines for future analyses of cross-body coordination using mutants, morphants, and transgenic approaches

Glucagon-like peptide 1 (GLP-1).

BACKGROUND: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. MAJOR CONCLUSIONS: Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders

Knowledge management: a review of the field and of OR's contribution

This paper examines the field of knowledge management (KM) and identifies the role of operational research (OR) in key milestones and in KM's future. With the presence of the OR Society journal Knowledge Management Research and Practice and with the INFORMS journal Organization Science, OR may be assumed to have an explicit and a leading role in KM. Unfortunately, the origins and the evidence of recent research efforts do not fully support this assumption. We argue that while OR has been inside many of the milestones there is no explicit recognition of its role and while OR research on KM has considerably increased in the last 5 years, it still forms a rather modest explicit contribution to KM research. Nevertheless, the depth of OR's experience in decision-making models and decision support systems, soft systems with hard systems and in risk management suggests that OR is uniquely placed to lead future KM developments. We suggest that a limiting aspect of whether OR will be seen to have a significant profile will be the extent to which developments are recognized as being informed by OR

O cuidado de enfermagem como prática empreendedora: oportunidades e possibilidades

OBJETIVOS: Compreender o significado do cuidado de enfermagem como prática social empreendedora. MÉTODOS: Foi baseada na Grounded Theory que, de forma sistemática, criativa e interativa possibilitou o desenvolvimento da teoria: "Vislumbrando o cuidado de enfermagem como prática social empreendedora". Amostra teórica constituiu-se de 35 sujeitos entrevistados, distribuídos em diferentes grupos amostrais. RESULTADOS: O cuidado de enfermagem como prática social empreendedora está associado ao sistema de relações e interações, à capacidade de interagir com os diferentes atores sociais, na capacidade de criar novos canais de comunicação e ações pró-ativas. CONCLUSÃO: A partir do cuidado como prática social empreendedora é possível atuar de forma pró-ativa, inovadora e participativa, sem desconsiderar as contradições sociais emergentes.OBJETIVO: Comprender el significado y desarrollar una teoría sustantiva sobre el cuidado de enfermería como una práctica social emprendedora. METODOS: Se basó en la Grounded Theory que, como un proceso sistemático, creativo e interactivo permitió el desarrollo de la teoría sustantiva: "Vislumbrando el cuidado de enfermería como una práctica social emprendedora". La muestra teórica estuvo constituida por treinta y cinco entrevistados distribuidos en diferentes grupos de muestras. RESULTADOS: El cuidado de enfermería como una práctica social emprendedora se asocia con el sistema de relaciones e interacciones, con la capacidad de interactuar con diferentes actores sociales y, con la capacidad de crear nuevos canales de comunicación y de acciones proactivas. CONCLUSIÓN: A partir del cuidado como una práctica emprendedora es posible actuar de manera proactiva, innovadora y participativa, sin dejar de lado las contradicciones sociales emergentes.OBJECTIVE: To understand the meaning and to develop a substantive theory about nursing care as an enterprising social practice. The METHODS: Was based on the Grounded Theory which, in a systematic, creative and interactive manner allowed the development of the substantive theory: "Realizing the nursing care as an enterprising social practice." The theoretical sample consisted of thirty-five subjects distributed among different groups of samples. RESULTS: The nursing care as an enterprising social practice is associated with the system of relationships and interactions, the ability to interact with different social actors and, the ability to create new channels of communication and proactive actions. CONCLUSION: Considering the care as an enterprising practice is possible to act in a proactive, innovative and participatory way, without neglecting the emerging aspects of social contradictions

Advances in modelling of biomimetic fluid flow at different scales

The biomimetic flow at different scales has been discussed at length. The need of looking into the biological surfaces and morphologies and both geometrical and physical similarities to imitate the technological products and processes has been emphasized. The complex fluid flow and heat transfer problems, the fluid-interface and the physics involved at multiscale and macro-, meso-, micro- and nano-scales have been discussed. The flow and heat transfer simulation is done by various CFD solvers including Navier-Stokes and energy equations, lattice Boltzmann method and molecular dynamics method. Combined continuum-molecular dynamics method is also reviewed