44 research outputs found

    Heterologous hyperimmune polyclonal antibodies against SARS-COV-2: A broad coverage, affordable, and scalable potential immunotherapy for Covid-19

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    The emergence and dissemination of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic triggered a global public health crisis. Although several SARS-CoV-2 vaccines have been developed, demand far exceeds supply, access to them is inequitable, and thus, populations in low- and middle-income countries are unlikely to be protected soon (1). Furthermore, there are no specific therapies available, which is a challenge for COVID-19 patient care (2). Thus, the appearance of SARS-CoV-2 variants and reports of reinfections associated with immune escape (3, 4) highlight the urgent need for effective and broad coverage COVID-19 therapeutics. Intravenous administration of human or heterologous antibodies is a therapy successfully used in patients with viral respiratory diseases (5). Accordingly, formulations containing SARS-CoV-2 specific antibodies are an attractive therapeutic option for COVID-19 patients (6). SARS-CoV-2 specific antibodies could limit infection by direct virion neutralization and/or by targeting infected cells for elimination via complement or antibody-mediated cytotoxicity (6). Specific SARS-CoV-2 antibody-based therapeutics include convalescent plasma (CP), monoclonal antibodies (mAbs), human polyclonal IgG formulations purified from CP or transgenic animals, and heterologous hyperimmune polyclonal antibodies (pAbs) (6). Although the window for using antibody-based therapeutics varies, clinical data show that they are mainly effective if administered early after symptoms onset (6).Universidad de Costa Rica/[741-C0-198]/UCR/Costa RicaCaja Costarricense del Seguro Social/[]/CCSS/Costa RicaBanco Centroamericano de Integración Económica/[]/BCIE/Costa RicaGerman academic exchange services/[57592642]/DAAD/AlemaniaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de MedicinaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

    Infectious Diseases, Social, Economic and Political Crises, Anthropogenic Disasters and Beyond: Venezuela 2019 – Implications for Public Health and Travel Medicine

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    During last months, there have been a significant increase in the evidences showing the catastrophic health situation in Venezuela. There are multiple epidemics, increase in emerging and reemerging infectious, tropical and parasitic diseases as consequences of the social, economic and political crises, which would be considered today a clearly anthropogenic disaster. Venezuela is facing in 2019, the worse sanitary conditions, with multiple implications for public health and travel medicine. So far, from a global perspective, this situation will be an impediment for the achievement of the sustainable development goals (SDG) in 2030. In this multiauthor review, there is a comprehensive analysis of the situation for infectious diseases, non-communicable diseases, their impact in the Americas region, given the migration crisis as well as the comparative status of the SDG 2030. This discussion can provide input for prioritizing emerging health problems and establish a future agenda

    Infectious Diseases, Social, Economic and Political Crises, Anthropogenic Disasters and Beyond: Venezuela 2019 – Implications for Public Health and Travel Medicine

    Get PDF
    During last months, there have been a significant increase in the evidences showing the catastrophic health situation in Venezuela. There are multiple epidemics, increase in emerging and reemerging infectious, tropical and parasitic diseases as consequences of the social, economic and political crises, which would be considered today a clearly anthropogenic disaster. Venezuela is facing in 2019, the worse sanitary conditions, with multiple implications for public health and travel medicine. So far, from a global perspective, this situation will be an impediment for the achievement of the sustainable development goals (SDG) in 2030. In this multiauthor review, there is a comprehensive analysis of the situation for infectious diseases, non-communicable diseases, their impact in the Americas region, given the migration crisis as well as the comparative status of the SDG 2030. This discussion can provide input for prioritizing emerging health problems and establish a future agenda

    A cellular deficiency of gangliosides causes hypersensitivity to Clostridium perfringens phospholipase C

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    Clostridium perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in the pathogenesis of gas gangrene. Previously, a cellular UDP-Glc deficiency was related with a hypersensitivity to the cytotoxic effect of Cp-PLC. Because UDP-Glc is required in the synthesis of proteoglycans, N-linked glycoproteins, and glycosphingolipids, the role of these gly-coconjugates in the cellular sensitivity to Cp-PLC was studied. The cellular sensitivity to Cp-PLC was significantly enhanced by glycosphingolipid synthesis inhibitors, and a mutant cell line deficient in gangliosides was found to be hypersensitive to Cp-PLC. Gangliosides protected hypersensitive cells from the cytotoxic effect of Cp-PLC and prevented its membrane-disrupting effect on artificial membranes. Removal of sialic acids by C. perfringens sialidase increases the sensitivity of cultured cells to Cp-PLC and intramuscular co-injection of C. perfringens sialidase, and Cp-PLC in mice potentiates the myotoxic effect of the latter. This work demonstrated that a reduction in gangliosides renders cells more susceptible to the membrane damage caused by Cp-PLC and revealed a previously unrecognized synergism between Cp-PLC and C. perfringens sialidase, providing new insights toward understanding the pathogenesis of clostridial myonecrosis.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

    Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

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    Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

    Cómo linear la estrategia de los colaboradores con la estrategia de la empresa

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    Tesis (Ingeniero Comercial)Uno de los grandes temas en actualidad empresarial es el que refiere a "Estrategia de Negocios". Durante el desarrollo de los negocios a través de la historia han existido etapas que han marcado esta actividad o, más bien, han separado su evolución en tres grandes períodos claramente definidos por Tofler en el planteo de las tres olas de la evolución de la economía. La primera hace referencia a la era agrícola, donde la economía era dependiente de la naturaleza; la segunda se refiere a la era industrial, donde pasó a ser dominante de la naturaleza y la tercera ola tiene que ver con tiempos contemporáneos basados en la información y comunicación, donde se considera interdependiente de la naturaleza. Hoy, el desarrollo económico y empresarial se encuentra en la tercera ola, es decir, la ola del conocimiento y la información. Esta era, en el ámbito de los negocios, se caracteriza por tener una fuerte competencia y una alta necesidad de adaptación al medio debido a los cambios tecnológicos determinados por la globalización actual. Con la fuerte competencia de los mercados actuales se ha incrementado el interés en la adquisición de bienes intangibles, tales como estrategias de creación de valor, relaciones con clientes, productos innovadores, procesos operativos de alta calidad, entre otros. Esto se debe a que son sistemas de gestión empresarial que adaptan el negocio al dinámico medio externo y optimizan las funciones administrativas, por lo tanto la estrategia del negocio se va a definir de acuerdo a las necesidades que tenga la empresa para subsistir dentro del mercado actual. "Lo único que no se ha podido mecanizar en el área del negocio es el hombre". Desde que la revolución industrial llevó al área del negocio a un claro desarrollo en términos de producción masiva, los hombres (mano de obra) perdieron participación como parte de la empresa. A medida que ha pasado el tiempo este fenómeno ha cobrado relevancia, ya que hoy es cada vez más necesario optimizar los costos de producción y gestión dada la fuerte competencia empresarial que existe. Pero hasta que punto se puede reemplazar el hombre por un computador o máquina? Esta pregunta representa la real importancia del tema abordado

    Membrane-damaging and cytotoxic sphingomyelinases and phospholipases

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    This chapter presents an overview of the classification, structure, and main physiopathological activities of bacterial sphingomyelinases and phospholipases, providing examples of their roles as virulence factors in several human and animal diseases. Bacterial sphingomyelinases (SMases) and phospholipases (PLases) constitute a heterogeneous group of surface-associated or secreted esterases produced by a variety of intracellular and extracellular pathogens. These enzymes might favor in different ways tissue colonization establishment and progression of the infection, or evasion of the immune response. In several cases, mutant bacterial strains lacking a sphingomyelinase or a phospholipase encoding gene have impaired virulence in experimental animals, demonstrating the role of these enzymes in pathogenicity. However, PLases contribute also to other aspects of bacterial lifestyle, including survival in different environments, and competition with other microorganisms; thus, the multifunctional nature of these enzymes reflects the remarkable adaptability of some bacteria.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)UCR::Vicerrectoría de Docencia::Salud::Facultad de MicrobiologíaUCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin

    Analgo-sedación con remifentanil para la intubación vigil con el laringoscopio retromolar de Bonfils

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    Introducción: se considera la intubación del paciente despierto como el método fundamental para asegurar el acceso a la vía respiratoria difícil sospechada. Para afrontar esta situación se han desarrollado nuevos dispositivos como el fibroscopio retromolar de Bonfils. Los analgésicos de acción corta y fácilmente evaluables, como el remifentanil, son elecciones excelentes para alcanzar este objetivo. Resulta importante su dosificación ya que no está desprovisto de efectos adversos. Objetivos: determinar la concentración plasmática de remifentanil que garantice un efecto analgo-sedativo óptimo para la intubación vigil con el laringoscopio retromolar de Bonfils. Métodos: se realizó un estudio descriptivo, en la Clínica Central «Cira García». La muestra quedó constituida por 12 pacientes programados para cirugía espinal cervical que requirieron intubación orotraqueal debido a su incapacidad de extender el cuello. Resultados: el tiempo medio para lograr el adecuado estado de conciencia con el método anestésico empleado fue 14 ± 5,8 min. La saturación de oxígeno descendió hasta una media de 94,2 ± 5,8 %. Los valores de tensión arterial media (TAM), frecuencia cardiaca (FC) y frecuencia espiratoria (FR) fueron 100,7 ± 17 mmHg, 77,6 ± 9,8. min-1 y 13,9 ±39 min-1 respectivamente. Presentaron recuerdos durante el procedimiento 4 pacientes, que refirieron estar satisfechos con el proceder. La concentración plasmática (Cp) de remifentanil calculada, necesaria para tener condiciones de intubación apropiadas fue de 0,0027 ± 0,005 µg/mL. Conclusiones: el empleo de remifentanil en dosis adecuadamente calculadas para alcanzar el efecto analgo-sedativo, para abordar la vía respiratoria difícil con el fibroscopio retromolar de Bonfils, en pacientes despiertos, fue una estrategia apropiada. </p
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