Browsing by Author "Rojas, Diego"
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Item A Chilean Experience of Telestroke in a COVID-19 Pandemic Year(2022) Delfino, Carlos; Mazzon, Enrico; Cavada, Gabriel; Muñoz Venturelli, Paula; Brunser, Alejandro; Jurado, Felipe; Lara, Lorena; Rocha, Diego; Arévalo, Mirya; Rojas, Diego; Mansilla, EloyBackground and purpose: Telemedicine for stroke patients' care (telestroke [TS]) has grown notably in recent decades and may offer advantages during health crisis. Hospital admissions related to stroke have decreased globally during the COVID-19 pandemic, but scarce information is available regarding the effect of COVID-19 in TS. Using a population-based TS registry, we investigated the impact of the first year of the COVID-19 pandemic throughout our TS network in Santiago, Chile. Methods: Stroke codes evaluated after the onset of COVID-19 restrictions in Chile (defined as March 15, 2020) were compared with those evaluated in 2019. We analyzed differences between number of stroke codes, thrombolysis rate, stroke severity, and time from the stroke onset to hospital admission. Results: We observed that the number of stroke codes and the number of patients undergoing reperfusion therapy did not change significantly (p = 0.669 and 0.415, respectively). No differences were found with respect to the median time from the stroke onset to admission (p = 0.581) or in National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.055). The decision-making-to-needle time was significantly shorter in the COVID-19 period (median 5 min [IQR 3-8], p < 0.016), but no significant changes were found at the other times. Conclusions: This study demonstrates the potential of adapting TS to extreme situations such as the COVID-19 pandemic, as well as the importance of establishing networks that facilitate patient access to quality treatments.Publication Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route(2024) Suárez, Cristian; Jara, José; Cortés, Gonzalo; Rojas, Diego; Araya, Gabriel; Molina, Alfredo; González, Fabiola; Fuentes, Sebastián; Aránguiz, Pablo; Campodónico, Paola; Maya, Juan; Vivar, Raúl; Catalán, MabelColorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC-such as 5-fluorouracil (5FU)-remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.Item Breaking Down Barriers: Easter Island's First Telestroke Thrombolysis Experience and Case Report(2022) Mazzon, Enrico; Arévalo, Mirya; Mirelis, Samuel; Delfino, Carlos; Rojas, Diego; Lara, Luis; Cárcamo, Daniel; Jurado, Felipe; Rocha, Diego; Muñoz, Paula; Mansilla, EloyEaster Island (Rapa Nui), Chile, is remote, located in the Polynesian Triangle in Oceania. The closest continental point is Chile, 3,512 km east. It has a population of 7,750 inhabitants, who are Chilean citizens, and receives more than 60,000 tourists a year. For this entire population, there is a medium complexity hospital without a neurology specialist. In 2019, local professionals were trained in a Telestroke program with remote clinical support conducted by neurologists located on mainland Chile. We present a 50-year-old native male, with unknown medical history, who suddenly presented right-half-body weakness and aphasia. He was evaluated via Telestroke consultation, and thrombolysis with tenecteplase was indicated. The patient improved rapidly and 45 min later the NIHSS score was 0 points. To our knowledge, this is the first reported case of Telestroke treatment in such a remote area, highlighting the importance of telemedicine to overcome geographical and technological stroke care barriers and to improve patients' outcome, no matter where they live.Item Neuronal Rubicon Represses Extracellular APP/Amyloid β Deposition in Alzheimer’s Disease(2022) Espinoza, Sandra; Grunenwald, Felipe; Gomez, Wileidy; García, Felipe; Abarzúa, Lorena; Oyarce, Sebastián; Hernández, María; Cortés, Bastián; Uhrig, Markus; Ponce, Daniela; Durán, Claudia; Hetz, Claudio; SanMartín, Carol; Cornejo, Victor; Ezquer, Fernando; Parra, Valentina; Behrens, María; Manque, Patricio; Rojas, Diego; Vidal, René; Woehlbier, Ute; Nassif, MelissaAlzheimer’s disease (AD) is the most prevalent age-associated neurodegenerative disease. A decrease in autophagy during aging contributes to brain disorders by accumulating potentially toxic substrates in neurons. Rubicon is a well-established inhibitor of autophagy in all cells. However, Rubicon participates in different pathways depending on cell type, and little information is currently available on neuronal Rubicon’s role in the AD context. Here, we investigated the cell-specific expression of Rubicon in postmortem brain samples from AD patients and 5xFAD mice and its impact on amyloid β burden in vivo and neuroblastoma cells. Further, we assessed Rubicon levels in human-induced pluripotent stem cells (hiPSCs), derived from early-to-moderate AD and in postmortem samples from severe AD patients. We found increased Rubicon levels in AD-hiPSCs and postmortem samples and a notable Rubicon localization in neurons. In AD transgenic mice lacking Rubicon, we observed intensified amyloid β burden in the hippocampus and decreased Pacer and p62 levels. In APP-expressing neuroblastoma cells, increased APP/amyloid β secretion in the medium was found when Rubicon was absent, which was not observed in cells depleted of Atg5, essential for autophagy, or Rab27a, required for exosome secretion. Our results propose an uncharacterized role of Rubicon on APP/amyloid β homeostasis, in which neuronal Rubicon is a repressor of APP/amyloid β secretion, defining a new way to target AD and other similar diseases therapeuticallyItem Telestroke in Chile: 1 year experience at 7 hospitals(2019) Mansilla, Eloy; Mazzon, Enrico; Jurado, Felipe; Lara, Lorena; Arévalo, Mirya; Rojas, Diego; Stephens, Gloria; Hoppe, Arnold; Brunser, AlejandroBackground: Acute ischemic stroke (AIS) is one of the leading causes of death in Chile. Intravenous thrombolysis (IVT) is an effective treatment. Geographical barriers and lack of specialists limit its application. Telemedicine can overcome some of these pitfalls. Aim: To describe the implementation and results of AIS treatment by telemedicine at the TeleStroke Unit (TeleACV) of the Southern Metropolitan Health Service, connected with seven hospitals in Chile. Material and methods: Descriptive analysis of a prospective tele-thrombolysis data-base that covers from 2016 to 2018, with an emphasis in the last year. Results: During the analyzed period, seven remote telemedicine centers were activated as far as 830 kilometers on a continental level from the reference center and up to 3,700 kilometers on an island level. There were 1,024 telemedicine consultations, 144 (14%) of them resulted in an IVT treatment. During 2018, 597 tele-consultations were made, thrombolysis was done in 115 (19%) patients aged 66+-13 years; 54 (46.6%) being female. The median admission National Institute of Health Stroke Scale was 8 (interquartile range (IQR) 5-14). The median door-to-needle time was 56.5 (IQR 44.8-73.3) minutes; 60% of patients were treated within 60 minutes. Eight patients (7%) were referred for a subsequent mechanical thrombectomy to a center of greater complexity. Symptomatic intra-cranial hemorrhages occurred in four treated patients (4%). One patient had a systemic bleeding. Conclusions: The Telestroke Unit achieved a high rate of IVT and good door-to-needle times. This may help to overcome some of the geographic barriers and the specialist availability gap in our country.