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Malformations in the development of the neural tube have been described to be associated with different aetiologies, such as genetic factors, toxic plants, chemical products, viral agents, or hyperthermia. A twenty-four-year-old female Eurasian brown bear (Ursus arctos arctos), permanently in captivity and kept under food and management control, gave birth to a stillborn cub at the end of gestation. Several malformations resulting from the anomalous development of the neural tube, not previously reported in bears, were observed, such as anencephaly, hypoplasia, micromyelia, severe myelodysplasia, syringomyelia, and spina bifida. Multiple canal defects (e.g., absence) were also observed in the spinal cord. In some regions, the intradural nerve roots surrounded the spinal cord in a diffuse and continuous way. The aetiology remains unidentified, although the advanced age of the mother and/or folic acid deficit might have been the possible causes of this disorder. Supplements of folate given to the mother before and during early pregnancy may have reduced the incidence of neural tube defects. That supplementation should be considered when the reproduction of bears is to occur in captivity, in order to prevent the loss of future generations of this endangered species.
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INTRODUCTION: Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI. METHODS AND ANALYSIS: The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266â mg capsules (Hidroferol SGC)/15â days or placebo on a 2:1 basis during 12â months. PRIMARY OBJECTIVE: to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI). SECONDARY OBJECTIVES: change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI. ETHICS AND DISSEMINATION: This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP)) requirements, ethical principles of the Declaration of Helsinki and national laws. The results will be submitted to indexed medical journals and national and international meetings. TRIAL REGISTRATION NUMBER: NCT02548364; Pre-results.
Asunto(s)
Biomarcadores/sangre , Calcifediol/administración & dosificación , Calcifediol/sangre , Infarto del Miocardio con Elevación del ST/terapia , Remodelación Ventricular/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Angioplastia Coronaria con Balón , Quimiocina CCL2/sangre , Método Doble Ciego , Femenino , Factor-23 de Crecimiento de Fibroblastos , Corazón/diagnóstico por imagen , Corazón/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Proyectos de Investigación , EspañaRESUMEN
In recent years, it has become evident that the level of guideline adherence in patients presenting with acute coronary syndrome (ACS) is highly correlated with patient outcomes. Unfortunately, guideline adherence is low in some geographic areas and especially in those patients at high-risk. Regional networks including ambulance systems and hospitals with catheterization laboratories are able to increase guideline adherence and patient outcomes by streamlining the critical pre- and intra-hospital processes as well as improving timely access to invasive procedures and recommended medication. Successful organization of an ACS network requires engagement of multiple stakeholders to create effective solutions for the specific local setting. There is no 'one-size-fits all' strategy to set-up and successfully run an ACS network. We present a framework for how to set up and organize an effective ACS network, delivering guideline-based care to improve patient outcomes.
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Síndrome Coronario Agudo/terapia , Prestación Integrada de Atención de Salud/organización & administración , Prestación Integrada de Atención de Salud/normas , Adhesión a Directriz , Austria , Humanos , Minnesota , Infarto del Miocardio/terapia , Países Bajos , North Carolina , Indicadores de Calidad de la Atención de Salud , Prevención Secundaria , Resultado del TratamientoRESUMEN
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 actions.
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Cardiotónicos/farmacología , Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/tratamiento farmacológico , Péptido 1 Similar al Glucagón/fisiología , Insulina/fisiología , Pirazinas/farmacología , Triazoles/farmacología , Animales , Apoptosis , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/etiología , Cardiomegalia/metabolismo , Cardiotónicos/uso terapéutico , Células Cultivadas , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatías Diabéticas/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Fibroblastos/fisiología , Fibronectinas/metabolismo , Fibrosis , Péptido 1 Similar al Glucagón/farmacología , Intolerancia a la Glucosa/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Masculino , Metformina/farmacología , Metformina/uso terapéutico , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , PPAR delta/metabolismo , Isoformas de Proteínas/farmacología , Isoformas de Proteínas/fisiología , Pirazinas/uso terapéutico , Ratas , Fosfato de Sitagliptina , Triazoles/uso terapéuticoRESUMEN
The plasma of patients with stable carotid atherosclerosis (n = 9), and healthy subjects (n = 10) have been fingerprinted with both GC-MS and (1)H NMR. Principal component analysis (PCA), partial least-squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA) have been applied to the profiles from each technique both separately and in combination. These techniques complement each other and enable a clearer picture of the biological samples to be interpreted not only for classification purposes, but also more importantly to define the metabolic state of patients with carotid atherosclerosis. The results showed at least 24 metabolites that were significantly modified in the group of atherosclerotic patients by this nontargeted procedure. Most of the changes can be associated to alterations of the metabolism characteristics of insulin resistance that can be strongly related to the metabolic syndrome. In addition, correlations among variables accounting for the classification show amino acids as variables whose changes showed a high degree of correlation. GC-MS and (1)H NMR fingerprints can provide complementary information in the identification of altered metabolic pathways in patients with carotid atherosclerosis. Moreover, correlations among the results with both techniques, instead of a single study, can provide a deeper insight into the patient state.
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Aterosclerosis/metabolismo , Metaboloma , Metabolómica/métodos , Aminoácidos/análisis , Estudios de Casos y Controles , Análisis Discriminante , Cromatografía de Gases y Espectrometría de Masas , Humanos , Resistencia a la Insulina , Espectroscopía de Resonancia Magnética , Síndrome Metabólico/metabolismo , Análisis de Componente PrincipalRESUMEN
Aggressive treatment with high-dose atorvastatin reduces more effectively the incidence of cardiovascular events than moderate statin therapy. The mechanism of this benefit has not been fully elucidated. In order to know the potential effects of statin treatment on the protein expression of circulating monocytes in acute coronary syndrome (ACS) patients, a proteomic analysis of these cells was carried out by 2-DE and MS. Twenty-five patients with non-ST-elevation acute coronary syndrome (NSTEACS) were randomized, the fourth day after admission, to receive ATV 80 mg/dL (n = 14) or conventional treatment (CT) (n = 11), for two months. Blood was withdrawn at the end of the treatment, and monocytes were extracted for proteomic analysis and their protein expression patterns determined. Age, sex, total cholesterol, LDL, HDL, triglycerides, body mass index, presence of hypertension, diabetes, and smoking status were not significantly different between the two groups of patients. The expression of 20 proteins was modified by intensive ATV. Among the most relevant results stand out the normalization by intensive ATV treatment of the expression of proteins that modulate inflammation and thrombosis such as protein disulfide isomerase ER60 (PDI), Annexin I, and prohibitin, or that have other protective effects as HSP-70. Thus, this approach shed light at the molecular level of the beneficial mechanisms of anti-atherothrombotic drugs.
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Síndrome Coronario Agudo/metabolismo , Anticolesterolemiantes/farmacología , Expresión Génica/efectos de los fármacos , Ácidos Heptanoicos/farmacología , Monocitos/metabolismo , Pirroles/farmacología , Síndrome Coronario Agudo/tratamiento farmacológico , Anciano , Anticolesterolemiantes/uso terapéutico , Atorvastatina , Distribución de Chi-Cuadrado , Relación Dosis-Respuesta a Droga , Electroforesis en Gel Bidimensional , Femenino , Perfilación de la Expresión Génica , Proteínas de Choque Térmico/metabolismo , Ácidos Heptanoicos/uso terapéutico , Humanos , Inflamación/metabolismo , Lípidos/sangre , Masculino , Persona de Mediana Edad , Pirroles/uso terapéutico , Estadísticas no Paramétricas , Espectrometría de Masas en Tándem , Trombosis/metabolismoRESUMEN
BACKGROUND AND PURPOSE: To investigate the effect of short-term high-dose atorvastatin on blood and plaque inflammation in patients with carotid stenosis. METHODS: Twenty patients undergoing carotid endarterectomy without previous statin treatment were randomized to receive either atorvastatin 80 mg/d (n=11) or no statins (n=9) for 1 month. We studied inflammatory mediators in plasma (enzyme-linked immunosorbent assay), peripheral blood mononuclear cells (PBMCs; quantitative RT-PCR and EMSA) and plaques (immunohistochemistry and Southwestern histochemistry). RESULTS: Atorvastatin significantly decreased total and low-density lipoprotein cholesterol and prostaglandin E2 plasma levels. PBMCs from treated patients showed impaired NF-kappaB activation and MCP-1 and COX-2 mRNA expression. Carotid atherosclerotic plaques demonstrated a significant reduction in macrophage infiltration, activated NF-kappaB, and COX-2 and MCP-1 expression. CONCLUSIONS: Intensive treatment with atorvastatin decreases inflammatory activity of PBMCs and carotid atherosclerotic plaques in 1 month. These data strongly suggest that the antiinflammatory effect of high doses of statins in humans can be seen very early.
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Aterosclerosis/tratamiento farmacológico , Ácidos Heptanoicos/uso terapéutico , Inflamación/tratamiento farmacológico , Leucocitos Mononucleares/citología , Pirroles/uso terapéutico , Anciano , Antiinflamatorios/farmacología , Atorvastatina , Southern Blotting , Western Blotting , Arterias Carótidas/patología , Quimiocina CCL2/metabolismo , Ciclooxigenasa 2/metabolismo , Dinoprostona/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Leucocitos Mononucleares/metabolismo , Lípidos , Masculino , Persona de Mediana Edad , FN-kappa B/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Se informan 4 casos que presentan el síndrome maligno por neurolépticos asistidos en nuestro servicio. Se hace una revisión de la entidad y se comparan nuestros hallazgos con la bibliografía médica consultada. En los resultados del trabajo se preconiza por primera vez el uso de nifedipina en el tratamiento de dicha afección
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Adulto , Humanos , Femenino , Masculino , Síndrome Neuroléptico Maligno/tratamiento farmacológico , Nifedipino/uso terapéuticoRESUMEN
Se informan 4 casos que presentan el síndrome maligno por neurolépticos asistidos en nuestro servicio. Se hace una revisión de la entidad y se comparan nuestros hallazgos con la bibliografía médica consultada. En los resultados del trabajo se preconiza por primera vez el uso de nifedipina en el tratamiento de dicha afección