Establishment and characterisation of a new cell line derived from Culex quinquefasciatus (Diptera: Culicidae)

Insect cell cultures are an important biotechnological tool for basic and applied studies. The objective of this work was to establish and characterise a new cell line from Culex quinquefasciatus embryonic tissues. Embryonated eggs were taken as a source of tissue to make explants that were seeded in L-15, Grace's, Grace's/L-15, MM/VP12, Schneider's and DMEM culture media with a pH range from 6.7-6.9 and incubated at 28ºC. The morphological, cytogenetic, biochemical and molecular characteristics of the cell cultures were examined by observing the cell shapes, obtaining the karyotypes, using a cellulose-acetate electrophoretic system and performing random amplified polymorphic DNA-polymerase chain reaction analysis, respectively. The Grace's/L-15 medium provided the optimal nutritional conditions for cell adhesion and proliferation. Approximately 40-60 days following the explant procedure, a confluent monolayer was formed. Cellular morphology in the primary cultures and the subcultures was heterogeneous, but in the monolayer the epithelioid morphology type predominated. A karyotype with a diploid number of six chromosomes (2n = 6) was observed. Isoenzymatic and molecular patterns of the mosquito cell cultures matched those obtained from the immature and adult forms of the same species. Eighteen subcultures were generated. These cell cultures potentially constitute a useful tool for use in biomedical applications.

La notificación on line de reacciones adversas a medicamentos, un avance de la Web del Centro Andaluz de Farmacovigilancia

Boletín semanal para profesionales sanitarios de la Secretaría General de Salud Pública y Participación Social de la Consejería de Salud

Long-term prognostic value of single-photon emission computed tomography myocardial perfusion imaging in diabetic patients with and without coronary artery disease

Keywords Diabetes mellitus; coronary artery disease; myocardial ischemia; prognostic value; single-photon emission computed tomography myocardial perfusion imaging Summary Aim: To determine the long-term prognostic value of SPECT myocardial perfusion imaging (MPI) for the occurrence of cardiovascular events in diabetic patients. Methods: SPECT MPI of 210 consecutive Caucasian diabetic patients were analysed using Kaplan-Meier event-free survival curves and independent predictors were determined by Cox multivariate analyses. Results: Follow-up was complete in 200 (95%) patients with a median period of 3.0 years (0.8-5.0). The population was composed of 114 (57%) men, age 65±10 years, 181 (90.5%) type 2 diabetes mellitus, 50 (25%) with a history of coronary artery disease (CAD) and 98 (49%) presenting chest pain prior to MPI. The prevalence of abnormal MPI was 58%. Patients with a normal MPI had neither cardiac death, nor myocardial infarction, independently of a history of coronary artery disease or chest pain. Among the independent predictors of cardiac death and myocardial infarction, the strongest was abnormal MPI (p<.0001), followed by history of CAD (Hazard Ratio (HR)= t 5.9, p=0.0001), diabetic retinopathy (HR=10.0, p=0.001) and inability to exercise (HR=7.7, p=0.02). Patients with normal 1VIPI had a low revascularisation rate of 2.4% during the follow-up period. Compared to normal MPI, cardiovascular events increased 5.2 fold for reversible defects, 8.5 fold for fixed defects and 20.1 fold for the association of both defects. Conclusion: Diabetic patients with normal MPI had an excellent prognosis independently of history of CAD. On the opposite, an abnormal MPI led to a > 5 fold increase in cardiovascular events. This emphasizes the value of SPECT MPI in predicting and risk-stratifying cardiovascular events in diabetic patients. Mots-Clés Diabète; maladie coronarienne; ischémie myocardique; valeur pronostique; tomoscintigraphie myocardique de perfusion par émission monophotonique Résumé Objectifs: Déterminer la valeur pronostique à long terme de la tomoscintigraphie myocardique de perfusion (TSMP) chez les patients diabétiques pour prédire les événements cardiovasculaires (ECV). Méthodes: Etude de 210 diabétiques caucasiens consécutifs référés pour une TSMP. Les courbes de survie ont été déterminées par Kaplan-Meier et les facteurs prédictifs indépendants par analyses multivariées de type Cox. Résultats: Le suivi a été complet chez 200 (95%) patients avec une durée médiane de 3.0 ans (0.8-50). La population était composée de 114 (57%) hommes, âge moyen 65±10 ans, avec 181 (90.5%) diabète de type 2, 50 (25%) antécédents de maladie coronarienne (AMC) et 98 (49%) patients connus pour un angor avant la TSMP. La prévalence de TSMP anormales était de 58%. Aucun décès d'origine cardiaque ou infarctus du myocarde n'est survenu chez les patients avec une TSMP normale, ceci indépendamment de leurs AMC et des douleurs thoraciques. Les facteurs prédictifs indépendants pour les ECV sont une TSMP anormale (p<.0001), les AMC (Hazard Ratio (HR)=15.9, p-0.0001), suivi de la rétinopathie diabétique (HR-10.0, p=0.001) et de l'incapacité à effectuer un exercice (HR=7.7, p=0.02). Les patients avec une TSMP normale ont présenté un taux de revascularisations de 2.4%. La présence de défauts mixtes accroît le risque d'ECV de 20.1 fois, les défauts fixes de 8.5 fois et les défauts réversibles de 5.2 fois comparés aux sujets avec une TSMP normale. Conclusion: Les patients diabétiques, coronariens ou non, avec une tomoscintigraphie myocardique de perfusion normale ont un excellent pronostique. A l'opposé, une TSMP anormale est associée à une augmentation du risque d'ECV de plus de 5 fois. Ceci confirme l'utilité de la TSMP dans la stratification du risque chez les patients diabétiques.

A population-based study of first and second-line drug-resistant tuberculosis in a high-burden area of the Mexico/United States border

The resistance of 139 Mycobacterium tuberculosis (MTB) isolates from the city of Monterrey, Northeast Mexico, to first and second-line anti-TB drugs was analysed. A total of 73 isolates were susceptible and 66 were resistant to anti-TB drugs. Monoresistance to streptomycin, isoniazid (INH) and ethambutol was observed in 29 cases. Resistance to INH was found in 52 cases and in 29 cases INH resistance was combined with resistance to two or three drugs. A total of 24 isolates were multidrug-resistant (MDR) resistant to at least INH and rifampicin and 11 MDR cases were resistant to five drugs. The proportion of MDR-TB among new TB cases in our target population was 0.72% (1/139 cases). The proportion of MDR-TB among previously treated cases was 25.18% (35/139 cases). The 13 polyresistant and 24 MDR isolates were assayed against the following seven second-line drugs: amikacin (AMK), kanamycin (KAN), capreomycin (CAP), clofazimine (CLF), ethionamide (ETH), ofloxacin (OFL) and cycloserine (CLS). Resistance to CLF, OFL or CLS was not observed. Resistance was detected to ETH (10.80%) and to AMK (2.70%), KAN (2.70%) and CAP (2.70%). One isolate of MDR with primary resistance was also resistant to three second-line drugs. Monterrey has a high prevalence of MDR-TB among previously treated cases and extensively drug-resistant-MTB strains may soon appear.

A human astrocytoma cell line is highly susceptible to infection with Trypanosoma cruzi

Astrocytes play a vital role in neuronal protection, homeostasis, vascular interchange and the local immune response. Some viruses and parasites can cross the blood-brain barrier and infect glia. Trypanosoma cruzi, the aetiological agent of Chagas disease, can seriously compromise the central nervous system, mainly in immune-suppressed individuals, but also during the acute phase of the infection. In this report, the infective capacity of T. cruzi in a human astrocyte tumour-derived cell line was studied. Astrocytes exposed to trypomastigotes (1:10 ratio) produced intracellular amastigotes and new trypomastigotes emerged by day 4 post-infection (p.i.). At day 6 p.i., 93% of the cells were infected. Using flow cytometry, changes were observed in both the expression of major histocompatibility complex class I and II molecules and the chemokine secretion pattern of astrocytes exposed to the parasite. Blocking the low-density lipoprotein receptor on astrocytes did not reduce parasite intracellular infection. Thus, T. cruzi can infect astrocytes and modulate the immune response during central nervous system infection.

Role of Kras Status in Patients with Metastatic Colorectal Cancer Receiving First-Line Chemotherapy plus Bevacizumab: A TTD Group Cooperative Study

BACKGROUND In the MACRO study, patients with metastatic colorectal cancer (mCRC) were randomised to first-line treatment with 6 cycles of capecitabine and oxaliplatin (XELOX) plus bevacizumab followed by either single-agent bevacizumab or XELOX plus bevacizumab until disease progression. An additional retrospective analysis was performed to define the prognostic value of tumour KRAS status on progression-free survival (PFS), overall survival (OS) and response rates. METHODOLOGY/PRINCIPAL FINDINGS KRAS data (tumour KRAS status and type of mutation) were collected by questionnaire from participating centres that performed KRAS analyses. These data were then cross-referenced with efficacy data for relevant patients in the MACRO study database. KRAS status was analysed in 394 of the 480 patients (82.1%) in the MACRO study. Wild-type (WT) KRAS tumours were found in 219 patients (56%) and mutant (MT) KRAS in 175 patients (44%). Median PFS was 10.9 months for patients with WT KRAS and 9.4 months for patients with MT KRAS tumours (p=0.0038; HR: 1.40; 95% CI:1.12-1.77). The difference in OS was also significant: 26.7 months versus 18.0 months for WT versus MT KRAS, respectively (p=0.0002; HR: 1.55; 95% CI: 1.23-1.96). Univariate and multivariate analyses showed that KRAS was an independent variable for both PFS and OS. Responses were observed in 126 patients (57.5%) with WT KRAS tumours and 76 patients (43.4%) with MT KRAS tumours (p=0.0054; OR: 1.77; 95% CI: 1.18-2.64). CONCLUSIONS/SIGNIFICANCE This analysis of the MACRO study suggests a prognostic role for tumour KRAS status in patients with mCRC treated with XELOX plus bevacizumab. For both PFS and OS, KRAS status was an independent factor in univariate and multivariate analyses.

A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer.

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250 mg/m(2)/DXR 40 mg/m(2) every 3 weeks for schedule 1 and VFL 120 mg/m(2)/DXR 25 mg/m(2) days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.

Fluorodeoxyglucose-positron emission tomography scan-positive recurrent papillary thyroid cancer and the prognosis and implications for surgical management.

BACKGROUND To compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management. METHODS From a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared. RESULTS Between 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease. CONCLUSION Patients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.

Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial.

In Europe, the combination of plerixafor + granulocyte colony-stimulating factor is approved for the mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and myeloma whose cells mobilize poorly. The purpose of this study was to further assess the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization in European patients with lymphoma or myeloma. In this multicenter, open label, single-arm study, patients received granulocyte colony-stimulating factor (10 μg/kg/day) subcutaneously for 4 days; on the evening of day 4 they were given plerixafor (0.24 mg/kg) subcutaneously. Patients underwent apheresis on day 5 after a morning dose of granulocyte colony-stimulating factor. The primary study objective was to confirm the safety of mobilization with plerixafor. Secondary objectives included assessment of efficacy (apheresis yield, time to engraftment). The combination of plerixafor + granulocyte colony-stimulating factor was used to mobilize hematopoietic stem cells in 118 patients (90 with myeloma, 25 with non-Hodgkin's lymphoma, 3 with Hodgkin's disease). Treatment-emergent plerixafor-related adverse events were reported in 24 patients. Most adverse events occurred within 1 hour after injection, were grade 1 or 2 in severity and included gastrointestinal disorders or injection-site reactions. The minimum cell yield (≥ 2 × 10(6) CD34(+) cells/kg) was harvested in 98% of patients with myeloma and in 80% of those with non-Hodgkin's lymphoma in a median of one apheresis. The optimum cell dose (≥ 5 × 10(6) CD34(+) cells/kg for non-Hodgkin's lymphoma or ≥ 6 × 10(6) CD34(+) cells/kg for myeloma) was harvested in 89% of myeloma patients and 48% of non-Hodgkin's lymphoma patients. In this prospective, multicenter European study, mobilization with plerixafor + granulocyte colony-stimulating factor allowed the majority of patients with myeloma or non-Hodgkin's lymphoma to undergo transplantation with minimal toxicity, providing further data supporting the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma or myeloma.

Peritoneal carcinomatosis due to ovarian cancer: comparison between MDCT, MRI and positron emission tomography-computed tomography with F18-fluorodeoxyglucose

Purpose: To compare MDCT, MRI and 18F-FDG PET/CT for the detection of peritoneal carcinomatosis due to ovarian cancerMethods and Materials: Fifteen women (mean age 65±) with clinical suspicion of ovarian cancer and peritoneal carcinomatosis underwent MDCT, MRI and 18F-FDG PET/CT, simultaneously and shortly performed before surgery (delay 8.1± days). According to the peritoneal cancer index nine abdominopelvic regions were defined. We applied four scores of lesion size on MDCT and MR images, while the maximal standard uptake value (SUVmax) was measured on 18F-FDG PET/CT. Three sites of lymphadenopathy and posterobasal pleural carcinomatosis were also analyzed. First, one radiologist blindly and separately read MDCT and MR images, while one nuclear physician blindly read PET/CT images grading each lesion according to four diagnostic certitudes. Secondly, all the images were reviewed jointly and compared with histopathology. Receiver operating characteristics (ROC) analysis was performed.Results: Peritoneal implants were proven in ten women (75%). Altogether, 228 abdominopelvic sites were compared. Sensitivity and specificity for MDCT was 90.2% and 90.6%, for MRI 93.5% and 86.3%, and for 18F-FDG PET/CT 92.7% and 95.7%, respectively. ROC area under the curve were 0.93 for MDCT and MRI, and 0.96 for 18F-FDG PET/CT respectively. No significant differences (p=0.11) were found between the three modalities.Conclusion: Although MRI revealed to be the most sensitive and 18F-FDG PET/CT the most specific modality, no significant differences were shown between the three techniques.

Engineering the thermal emission of macroporous silicon

Todos los cuerpos emiten luz espontaneamente al ser calentados. El espectro de radiacion es una funcion de la temperatura y el material. Sin embargo, la mayoria de los materiales irradia, en general, en una banda espectral amplia. Algunas matereiales, por el contrario, son capaces de concentrar la radiacion termica en una banda espectral mucho mas estrecha. Estos materiales se conocen como emisores selectivos y su uso tiene un profundo impacto en la eficiencia de sistemas sistemas tales como iluminacion y conversion de energia termofotovoltaica. De los emisores selectivos se espera que sean capaces de operar a altas temperaturas y que emitan en una banda espectral muy concisa. Uno de los metodos mas prometedores para controlar y disenar el espectro de emision termico es la utilizacion de cristales fotonicos. Los cristales fotonicos son estructuras periodicas artificiales capaces de controlar y confinar la luz de formas sin precedentes. Sin embargo, la produccion de dichas estructuras con grandes superficies y capaces de soportar altas temperaturas sigue siendo una dificil tarea. Este trabajo esta dedicada al estudio de las propiedades de emision termica de estructuras 3D de silicio macroporoso en el rango espectral mid-IR (2-30 m). En particular, este trabajo se enfoca en reducir la elevada emisividad del silicio cristalino. Las muestras estudiadas en este trabajo tienen una periodicidad de 4 m, lo que limitan los resultados obtenidos a la banda del infrarrojo medio, aunque estructuras mucho mas pequenas son tecnologicamente realizables con el metodo de fabricacion utilizado. Hemos demostrado que el silicio macroporoso 3D puede inhibir completamente la emision termica en su superficie. Mas aun, esta banda se puede ajustar en un amplio margen mediante pequenos cambios durante la formacion de los macroporos. Tambien hemos demostrado que tanto el ancho como la frecuencia de la banda de inhibicion se puede doblar mediante la aplicacion de tecnicas de postprocesado adecuadas. Finalmente hemos mostrado que es posible crear bandas de baja emisividad arbitrariamente anchas mediante estructuras macroporosas aperiodicas.

Increased audiovisual integration in cochlear-implanted deaf patients: independent components analysis of longitudinal positron emission tomography data.

It has been demonstrated in earlier studies that patients with a cochlear implant have increased abilities for audio-visual integration because the crude information transmitted by the cochlear implant requires the persistent use of the complementary speech information from the visual channel. The brain network for these abilities needs to be clarified. We used an independent components analysis (ICA) of the activation (H2 (15) O) positron emission tomography data to explore occipito-temporal brain activity in post-lingually deaf patients with unilaterally implanted cochlear implants at several months post-implantation (T1), shortly after implantation (T0) and in normal hearing controls. In between-group analysis, patients at T1 had greater blood flow in the left middle temporal cortex as compared with T0 and normal hearing controls. In within-group analysis, patients at T0 had a task-related ICA component in the visual cortex, and patients at T1 had one task-related ICA component in the left middle temporal cortex and the other in the visual cortex. The time courses of temporal and visual activities during the positron emission tomography examination at T1 were highly correlated, meaning that synchronized integrative activity occurred. The greater involvement of the visual cortex and its close coupling with the temporal cortex at T1 confirm the importance of audio-visual integration in more experienced cochlear implant subjects at the cortical level.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). METHODS Treatment: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

El Discurso mediático sobre las tecnologías de la información y la comunicación :el caso de los periódicos on-line La Vanguardia y El Universal

Aproximació diagnòstica quantitativa-qualitativa per conèixer els termes sobre Tecnologies de la Informació i la Comunicació més usats per dos diaris en la seva versió en línia i estudiar com són concebuts i expressats en el discurs mediàtic. En els mitjans la majoria dels termes tecnològics usats tenen una significació discordant causa de la concepció imprecisa d'Internet per Web, concepció que no obeeix a una sinonímia sinó al generalitzat enteniment d'Internet com a mitjà de comunicació i no com a infraestructura, noció que reprèn i legitima l'ús merament instrumental de les Tecnologies de la Informació i la Comunicació a la societat.