Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila melanogaster

Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca 2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.Centro de Investigaciones CardiovascularesCentro de Investigaciones Inmunológicas Básicas y Aplicada

Outpatient Management of Malignant Pleural Effusion Using a Tunneled Pleural Catheter: Preliminary Experience

Inpatient management of malignant pleural effusion includes the placement of a conventional thoracostomy tube for drainage and talc slurry pleurodesis and/or a surgical approach consisting of video-assisted thoracoscopic talc insufflation. Both techniques require prolonged hospital stays of up to 1 week. Unfortunately, life expectancy in patients with this disease does not usually exceed 6 months, and so the primary aim of any palliative intervention intended to improve quality of life should be to avoid hospital admissions and to relieve pain as far as possible. Of the few outpatient alternatives to hospital management the most frequently used is repeated thoracentesis. We describe the outpatient management of malignant pleural effusion by placement of a tunneled pleural catheter in a patient with stage IIIB lung adenocarcinoma. In our opinion, the use of this catheter offers a viable alternative to conventional therapy and is better tolerated

Diagnostic yield of electromagnetic navigation bronchoscopy is highly dependent on the presence of a Bronchus sign on CT imaging: results from a prospective study

Electromagnetic navigation bronchoscopy (ENB) has been developed as a novel ancillary tool for the bronchoscopic diagnosis of pulmonary nodules. Despite successful navigation in 90% of patients, ENB diagnostic yield does not generally exceed 70%. We sought to determine whether the presence of a bronchus sign on CT imaging conditions diagnostic yield of ENB and might account for the discrepancy between successful navigation and diagnostic yield. METHODS: We conducted a prospective, single-center study of ENB in 51 consecutive patients with pulmonary nodules. ENB was chosen as the least invasive diagnostic technique in patients with a high surgical risk, suspected metastatic disease, or advanced-stage disease, or in those who demanded a preoperative diagnosis prior to undergoing curative resection. We studied patient and technical variables that might condition diagnostic yield, including size, cause, location, distance to the pleural surface, and fluorodeoxyglucose uptake of a given nodule; the presence of a bronchus sign on CT imaging; registration point divergence; and the minimum distance from the tip of the locatable guide to the nodule measured during the procedure. RESULTS: The diagnostic yield of ENB was 67% (34/51). The sensitivity and specificity of ENB for malignancy in this study were 71% and 100%, respectively. ENB was diagnostic in 79% (30/38) patients with a bronchus sign on CT imaging but only in 4/13 (31%) with no discernible bronchus sign. Univariate analysis identified the bronchus sign (P = .005) and nodule size (P = .04) as statistically significant variables conditioning yield, but on multivariate analysis, only the bronchus sign remained significant (OR, 7.6; 95% CI, 1.8-31.7). No procedure-related complications were observed. CONCLUSIONS: ENB diagnostic yield is highly dependent on the presence of a bronchus sign on CT imaging

A molecular portrait of high-grade ductal carcinoma in situ

Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty-two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM, and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor-intrinsic subtypes, proliferative, immune scores, and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like, or ERBB2 + ) displayed signatures characteristic of activated Treg cells (CD4 + /CD25 + /FOXP3 + ) and CTLA4 + /CD86 + complexes indicative of a tumor-associated immunosuppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly, ncRNA and methylation profiles reproduce changes observed postinvasion. Among the most significant findings, we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a preinvasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer.Centro de Investigaciones Inmunológicas Básicas y Aplicada

Factores alimentarios - nutricionales que afectan la calidad de vida de personas con HTA. Centro de Salud N° 9. Salta.

La relevancia clínica de la HTA reside en el incremento del riesgo de padecer ECV y por ende, en el deterioro de la calidad de vida de las personas que la padecen.\ud El objetivo es conocer factores de riesgo alimentario y nutricionales que afectan la calidad de vida de las personas con HTA, asisitidas el Centro de Salud Nº9 Villa Lavalle, Ciudad de Salta. Año 2010

Caracterización funcional del ARN largo no codificante en la LINC885 progresión del cáncer de mama

El objetivo del trabajo es determinar el rol del LINC885 sobre la proliferación celular, en modelos celulares mamarios humanos tipo normal y tumorales invasivo y no invasivo. Caracterizar al LINC885 como un biomarcador de progresión del cáncer de mama e identificar las posibles vías de señalización en que se encuentra involucrado.Facultad de Ciencias Médica

Aging and CaMKII alter intracellular Ca2+ transients and heart rhythm in Drosophila melanogaster

Aging is associated to disrupted contractility and rhythmicity, among other cardiovascular alterations. Drosophila melanogaster shows a pattern of aging similar to human beings and recapitulates the arrhythmogenic conditions found in the human heart. Moreover, the kinase CaMKII has been characterized as an important regulator of heart function and an arrhythmogenic molecule that participate in Ca2+ handling. Using a genetically engineered expressed Ca2+ indicator, we report changes in cardiac Ca 2+ handling at two different ages. Aging prolonged relaxation, reduced spontaneous heart rate (HR) and increased the occurrence of arrhythmias, ectopic beats and asystoles. Alignment between Drosophila melanogaster and human CaMKII showed a high degree of conservation and indicates that relevant phosphorylation sites in humans are also present in the fruit fly. Inhibition of CaMKII by KN-93 (CaMKII-specific inhibitor), reduced HR without significant changes in other parameters. By contrast, overexpression of CaMKII increased HR and reduced arrhythmias. Moreover, it increased fluorescence amplitude, maximal rate of rise of fluorescence and reduced time to peak fluorescence. These results suggest that CaMKII in Drosophila melanogaster acts directly on heart function and that increasing CaMKII expression levels could be beneficial to improve contractility.Centro de Investigaciones CardiovascularesCentro de Investigaciones Inmunológicas Básicas y Aplicada

Expresión génica diferencial de hipocampo en un modelo de envejecimiento cerebral tratado con terapia génica de largo plazo

Objetivos del trbajo: 1) Implementar terapia génica a largo plazo con un adenovector helper-dependent (HD) de última generación que expresa el gen del insulin-like growth factor I (IGF-I) en ratas viejas, las cuales se caracterizan por un significativo deficit cognitivo, a fin de restaurar su memoria espacial. 2) Analizar el transcriptoma hipocampal de animales viejos tratados, viejos controles y jóvenes controles comparando los diferentes perfiles de expresión génica a fin de detectar cambios asociados a la edad y al tratamiento con IGF-I transgénico.Facultad de Ciencias Médica

Expresión génica diferencial de hipocampo en un modelo de envejecimiento cerebral tratado con terapia génica de largo plazo

Objetivos del trbajo: 1) Implementar terapia génica a largo plazo con un adenovector helper-dependent (HD) de última generación que expresa el gen del insulin-like growth factor I (IGF-I) en ratas viejas, las cuales se caracterizan por un significativo deficit cognitivo, a fin de restaurar su memoria espacial. 2) Analizar el transcriptoma hipocampal de animales viejos tratados, viejos controles y jóvenes controles comparando los diferentes perfiles de expresión génica a fin de detectar cambios asociados a la edad y al tratamiento con IGF-I transgénico.Facultad de Ciencias Médica

Expresión génica diferencial de hipocampo en un modelo de envejecimiento cerebral tratado con terapia génica de largo plazo

Objetivos del trbajo: 1) Implementar terapia génica a largo plazo con un adenovector helper-dependent (HD) de última generación que expresa el gen del insulin-like growth factor I (IGF-I) en ratas viejas, las cuales se caracterizan por un significativo deficit cognitivo, a fin de restaurar su memoria espacial. 2) Analizar el transcriptoma hipocampal de animales viejos tratados, viejos controles y jóvenes controles comparando los diferentes perfiles de expresión génica a fin de detectar cambios asociados a la edad y al tratamiento con IGF-I transgénico.Facultad de Ciencias Médica