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OBJECTIVE: To estimate the prevalence of illicit tobacco trade (ITT) and different ITT modes-tax stamp counterfeiting and smuggling-in Argentina. DESIGN: Cross-sectional study using an empty tobacco pack survey with a simple random cluster sampling design. Classification as licit/illicit using forensic analysis of tax stamps and packs and econometric modelling. SETTING: Cities of Buenos Aires, La Matanza, Cordoba, Rosario, Mendoza, Neuquen, Posadas, Salta; January-June 2019. RESULTS: Of a total sample of 15 658 packs, 83.2% were manufactured in Argentina and 16.8% were foreign packs. Overall ITT prevalence-weighted by district population size-was estimated at 13.7%, where 6.1% was attributable to stamp counterfeiting-that is, a forged stamp not issued by the national tax authority-and 7.6% to contraband smuggling of foreign cigarette packs-that is, illicit trade of packs across national borders. CONCLUSIONS: The ITT problem in Argentina seems to be equally represented by counterfeiting of tobacco tax stamps on packs with domestic features and smuggling of foreign cigarette packs. Foreign cigarettes represent a minor component of the pack sampled in most of the country, except in Salta and Posadas, which are located close to the border with Paraguay. It is essential to implement an effective track-and-trace system including the monitoring of tax stamp authenticity and increase border control to block the entry of smuggled products, particularly from Paraguay. Reducing ITT is necessary to ensure the effectiveness of tobacco taxation measures.
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Nicotiana , Produtos do Tabaco , Argentina/epidemiologia , Cidades , Comércio , Estudos Transversais , Humanos , ImpostosRESUMO
Objective: To assess progress in and barriers to implementing bans on tobacco advertising, promotion and sponsorship (TAPS) in Uruguay, which has a complete ban, and Argentina, with a partial ban. Methods: Legislation on TAPS bans in Uruguay and Argentina was reviewed and relevant published literature, news stories, civil society reports and tobacco industry reports retrieved to analyze progress in implementing TAPS bans. Results: In Uruguay, the complete TAPS ban, which includes standardized tobacco packaging, maintains high compliance and severely limits exposure of TAPS, despite a few problems with corporate social responsibility, social media, and transnational advertising. In Argentina, the partial TAPS ban has more problems with compliance and exposure to TAPS. The most important barriers to implementing TAPS bans in both countries are the tobacco companies. In Uruguay, tobacco companies do not comply in a few areas but the complete ban greatly minimizes this. In Argentina, however, tobacco companies can more easily exploit gaps in the partial TAPS ban, such as advertising at the points of sale, promoting contests, and using influencers on social media. Conclusions: The partial TAPS ban in Argentina illustrates the problems with enforcement and the tobacco industry's ability to exploit loopholes and continue to market their products, especially to young people. A complete TAPS ban, including standardized tobacco packaging, as in Uruguay, is easier to implement and enforce and is effective in reducing exposure to tobacco advertising. Nevertheless, governments should prioritize implementing TAPS bans on social media, which remains a difficult sphere to monitor and allows tobacco companies to continue recruiting and targeting young people.
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Gem-Pro is a new tool for gene mining and functional profiling of bacteria. It initially identifies homologous genes using BLAST and then applies three filtering steps to select orthologous gene pairs. The first one uses BLAST score values to identify trivial paralogs. The second filter uses the shared identity percentages of found trivial paralogs as internal witnesses of non-orthology to set orthology cutoff values. The third filtering step uses conditional probabilities of orthology and non-orthology to define new cutoffs and generate supportive information of orthology assignations. Additionally, a subsidiary tool, called q-GeM, was also developed to mine traits of interest using logistic regression (LR) or linear discriminant analysis (LDA) classifiers. q-GeM is more efficient in the use of computing resources than Gem-Pro but needs an initial classified set of homologous genes in order to train LR and LDA classifiers. Hence, q-GeM could be used to analyze new set of strains with available genome sequences, without the need to rerun a complete Gem-Pro analysis. Finally, Gem-Pro and q-GeM perform a synteny analysis to evaluate the integrity and genomic arrangement of specific pathways of interest to infer their presence. The tools were applied to more than 2 million homologous pairs encoded by Bacillus strains generating statistical supported predictions of trait contents. The different patterns of encoded traits of interest were successfully used to perform a descriptive bacterial profiling.
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Bactérias/genética , Impressões Digitais de DNA/instrumentação , Genômica/métodos , Filogenia , Software , Bacillus/genética , Mineração de Dados/métodosRESUMO
The effect of different extenders on sperm motility and fertility was evaluated during liquid storage of ram semen at 5 °C and 15 °C. The semen was collected, pooled and diluted in three commercial extenders: Inra 96® (INRA) based on skimmed milk, Biladyl® A fraction (BIL) based on egg yolk, and Ovixcell® (OVIX) based on soybean lecithin. Then, sperm motility was evaluated at 0, 6, 24, 48, 72 and 96 h. In order to evaluate fertility, samples stored at 15 °C were used after dilution in INRA and OVIX. Results showed that progressive motility was significantly higher up to 72 h of storage in sperm samples maintained at 5 °C in comparison with 15 °C, similarly for each tested diluent. When samples were stored at 5 °C in OVIX, kinematic parameters such as velocity (except curvilinear velocity, VCL), trajectory [linearity (LIN), straightness (STR), wobble (WOB)], amplitude of lateral head displacement (ALH) and beat/cross frequency (BCF) were higher than in INRA and BIL. No significant differences in pregnancy rate were detected between INRA (62.6%) and OVIX (58.9%). In conclusion, liquid storage at 5 °C with OVIX extender is an interesting option since non-animal components are used, and this extender offers similar in vitro and in vivo efficacy as other extenders containing animal components.
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Criopreservação/veterinária , Fertilidade/efeitos dos fármacos , Preservação do Sêmen/veterinária , Sêmen/fisiologia , Carneiro Doméstico/fisiologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Animais , Sêmen/efeitos dos fármacos , Análise do Sêmen/veterinária , TemperaturaRESUMO
RATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES: To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. METHODS: Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. MEASUREMENTS AND MAIN RESULTS: Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. CONCLUSIONS: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.
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Fibrose Cística/complicações , Pneumopatias/etiologia , Criança , Pré-Escolar , Fibrose Cística/patologia , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Pulmão/patologia , Pneumopatias/patologia , Masculino , Testes de Função Respiratória , EspirometriaRESUMO
In May 2016, the executive branch of the Government of Argentina ratified Decree 626, which raised domestic taxes on cigarettes from 60% to 75%, amounting to a 50% increase in their average retail price. This measure was promoted by Argentina's InterAmerican Heart Foundation (FIC Argentina) through a strategy that included conducting local research to assess the measure's viability and impact; drafting a policy proposal; working in coordination with other national and international civil society organizations; pursuing collaborative incidence activities with key members of the national executive branch; and implementing a communications strategy. The uniqueness of each economic, social, political, and institutional context in the countries of the Region of the Americas makes it necessary to adapt policy to local conditions. The work experience of FIC Argentina serves as a roadmap for other organizations in the Region that seek to promote an increase in taxes on tobacco products or other policies designed to protect public health by adapting international recommendations and local evidence to each country's specific context. This article presents a series of lessons learned that may prove useful in other countries.
Em maio de 2016, as autoridades do poder executivo da Argentina sancionaram o Decreto 626 que determinou um aumento da tributação interna dos cigarros de 60% a 75%, implicando em um aumento de 50% no preço médio de venda ao consumidor. Esta medida foi apoiada pela Fundação Interamericana do Coração (FIC) Argentina que adotou uma estratégia que abrangeu a realização de pesquisas locais para determinar a viabilidade e o impacto de tal medida, a elaboração de uma proposta política, o trabalho em rede com outras organizações nacionais e internacionais da sociedade civil, ações colaborativas com representantes do poder executivo nacional e a implementação de uma campanha de comunicação. As particularidades dos contextos econômicos, sociais, políticos e institucionais de cada país da Região das Américas exigem que as propostas políticas se adéquem à realidade local. A experiência de trabalho realizado pela FIC Argentina serve de modelo a outras organizações que defendem o aumento da tributação dos cigarros e outras políticas de proteção da saúde pública, com a adaptação das recomendações internacionais ao contexto de cada país e o uso das evidências locais. Este artigo expõe uma série de ensinamentos que podem servir a outros países da Região.
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The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.
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Etnicidade/genética , Variação Genética , Genética Populacional , Fenótipo , Evolução Biológica , Feminino , Geografia , Humanos , América Latina , Masculino , Característica Quantitativa Herdável , AutoimagemRESUMO
INTRODUCTION: This work focuses on ammonia metabolism of Liver Microorgans (LMOs) after cold preservation in a normothermic reoxygenation system (NRS). We have previously reported the development of a novel preservation solution, Bes-Gluconate-PEG 35 kDa (BG35) that showed the same efficacy as ViaSpan to protect LMOs against cold preservation injury. The objective of this work was to study mRNA levels and activities of two key Urea Cycle enzymes, Carbamyl Phosphate Synthetase I (CPSI) and Ornithine Transcarbamylase (OTC), after preservation of LMOs in BG35 and ViaSpan and the ability of these tissue slices to detoxify an ammonia overload in a NRS model. MATERIAL AND METHODS: After 48 h of cold storage (0°C in BG35 or ViaSpan) LMOs were rewarmed in KHR containing an ammonium chloride overload (1 mM). We determined ammonium detoxification capacity (ADC), urea synthesis and enzyme activities and relative mRNA levels for CPSI and OTC. RESULTS: At the end of reoxygenation LMOs cold preserved in BG35 have ADC and urea synthesis similar to controls. ViaSpan group demonstrated a lower capacity to detoxify ammonia and to synthesize urea than fresh LMOs during the whole reoxygenation period which correlated with the lower mRNA levels and activities for CPSI and OTC observed for this group. CONCLUSION: We demonstrate that our preservation conditions (48 hours, BG35 solution, anoxia, 0ºC) did not affect ammonia metabolism of cold preserved LMOs maintaining the physiological and biochemical liver functions tested, which allows their future use as biological component of a BAL system.
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Amônia/metabolismo , Temperatura Baixa , Fígado/efeitos dos fármacos , Fígado/metabolismo , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos/métodos , Adenosina/farmacologia , Alopurinol/farmacologia , Animais , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Glutationa/farmacologia , Insulina/farmacologia , Fígado/patologia , Testes de Função Hepática , Masculino , Modelos Animais , Ornitina Carbamoiltransferase/metabolismo , Oxigênio/administração & dosagem , Oxigênio/metabolismo , RNA Mensageiro/metabolismo , Rafinose/farmacologia , Ratos , Ratos Wistar , Reperfusão , Fatores de TempoRESUMO
The choice of the best species to cultivate in semi-arid and arid climates is of fundamental importance, and is determined by many factors, including temperature and rainfall, soil type, water availability for irrigation and crop purposes. Soil or water salinity represents one of the major causes of crop stress. Species of the genus Atriplex are characterized by high biomass productivity, high tolerance to drought and salinity, and high efficiency in use of solar radiation and water. Based on a search of the international literature, the authors outline an agro-climatic zoning model to determine potential production areas in Argentina for Atriplex halimus and Atriplex numularia. Using the agroclimatic limits presented in this work, this model may be applied to any part of the world. When superimposed on the saline areas map, the agroclimatic map shows the suitability of agro-ecological zoning for both species for energy purposes on land unsuitable for food production. This innovative study was based on the implementation of a geographic information system that can be updated by further incorporation of complementary information, with consequent improvement of the original database.
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Atriplex/crescimento & desenvolvimento , Clima , Modelos Teóricos , Salinidade , Argentina , Biomassa , Chuva , TemperaturaRESUMO
Irritable bowel syndrome (IBS) and vitamin D deficiency are common among children in Latin America. Previous studies show that Bifidobacterium longum35624TM improves IBS symptoms in adults. This real-world, single-arm, open-label study conducted in Chile investigated the effects of B. longum 35624 (1 × 109 colony-forming units, 12 weeks) on gastrointestinal symptoms (adapted IBS severity scoring system [IBS-SSS]; adapted Questionnaire on Pediatric Gastrointestinal Symptoms [QPGS], and Bristol Stool Form Scale) in 64 children and adolescents (8-18 years) and explored the relationship with baseline vitamin D status. Improvements in all IBS-SSS domains and composite score were observed at week 6 and 12 (p < 0.0007 versus baseline), with 98.3% of participants experiencing numerical improvements in ≥3 domains. Clinically meaningful improvement was seen in 96.6% of participants. The distribution of IBS-SSS severity categories shifted from moderate/severe at baseline to mild/remission (p < 0.0001). Improvements were not maintained during the two-week washout. Low baseline serum vitamin D levels did not correlate to IBS severity or probiotic response. QPGS significantly decreased from baseline to week 6 (p = 0.0005) and 12 (p = 0.02). B. longum 35624 may improve IBS symptoms in children and adolescents, even those with vitamin D deficiency. A confirmatory randomized controlled trial and further exploration of probiotic response and vitamin D status are needed.
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Bifidobacterium longum , Síndrome do Intestino Irritável , Probióticos , Humanos , Síndrome do Intestino Irritável/microbiologia , Adolescente , Criança , Probióticos/uso terapêutico , Masculino , Feminino , Chile , Resultado do Tratamento , Índice de Gravidade de Doença , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
Background: There are limitations to predicting perinatal asphyxia, as current tools rely almost entirely on fetal cardiotocography (CTG). The fetal lack of responsiveness scale (FLORS) is a new diagnostic alternative based on the physiological phenomena associated with fetal hypoxia. Objectives: The objective of this study was to develop, validate, and assess the diagnostic accuracy of the FLORS for predicting severe perinatal hypoxia (SPH). Study Design: A two-phase retrospective observational cross-sectional analytical study was conducted. Phase 1 involved the formulation and retrospective validation of the FLORS. A total of 366 fetal CTG records were evaluated twice by seven readers. Phase 2 was a collaborative, retrospective, multicenter diagnostic test study that included 37 SPH and 366 non-SPH cases. Results: Phase 1: A numeric, physiology-based scale was developed and refined based on expert opinions. The median time to apply the scale per reading was 38 s. Cronbach's alpha, which is a reliability measure, was significant (p = 0.784). The kappa index for test-retest agreement was moderate to reasonable, with a median value of 0.642. For interobserver agreement, the kappa index per variable was as follows: baseline, 0.669; accelerations, 0.658; variability, 0.467; late/variable decelerations, 0.638; slow response decelerations, 0.617; and trend to change, 0.423. Phase 2, including 37 SPH and 366 non-SPH cases, showed a sensitivity of 62.2% and specificity of 75.4% for the 2-point score, whereas the 3-point score had a sensitivity of 35.1% and specificity of 89.9%. The area under the curve (AUC) was significant at 0.73 (CI 0.645-0.818). Conclusions: FLORS demonstrated significant internal consistency and observer agreement, with a promising sensitivity-specificity balance and significant AUC. Further research is needed to assess its impact on perinatal hypoxia and cesarean delivery.
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Cardiotocografia , Hipóxia Fetal , Humanos , Feminino , Estudos Transversais , Hipóxia Fetal/diagnóstico , Gravidez , Estudos Retrospectivos , Cardiotocografia/métodos , Reprodutibilidade dos Testes , Asfixia Neonatal/diagnóstico , Sensibilidade e Especificidade , Recém-Nascido , Frequência Cardíaca Fetal/fisiologia , AdultoRESUMO
Background: Descending necrotizing mediastinitis (DNM) is an acute life-threatening infection that originates in the oropharyngeal region. It is an uncommon disease with a mortality rate of about 20-40%. This high mortality is mainly attributed to delays in diagnosis and treatment and poor drainage of the mediastinum. We highlight key points that may help reduce mortality. Case Description: We analyze a retrospective case series of seven patients diagnosed with DNM between March 2019 and July 2022 at Hospital de la Santa Creu i Sant Pau. The primary oropharyngeal infection was peritonsillar abscess in three cases and odontogenic abscess in four. All patients showed symptoms of severe cervical infection and symptoms suggestive of mediastinitis. A cervicothoracic computed tomography (CT) scan confirmed the presence of cervical and mediastinal collections and emphysema in all cases. All patients were simultaneously evaluated by the otorhinolaryngology and thoracic surgery teams. Broad-spectrum antibiotic therapy was instituted pending culture. All the patients underwent urgent surgery, consisting of cervicotomy to control the cervical focus and unilateral or bilateral video-assisted thoracoscopic debridement and drain of the pleural cavities and mediastinum. Regarding the outcomes, no patients died, one patient (14.2%) underwent transcervical mediastino-thoracoscopy drainage only. In six patients (85.8%) we performed a combined transcervical and transthoracic approach. Reoperation was required in 3 (43%) cases. The parameter that indicated a poor clinical evolution in these patients was an increase in C-reactive protein and the infection extension on the cervicothoracic CT scan. The follow-up was 30 days from last surgery; there were no losses. Conclusions: Based on our experience, the key points that can help reduce the high mortality associated with DNM are a rapid multidisciplinary assessment and a combined surgical procedure, considering the minimally invasive approach as the first option to drain the pleural cavities and mediastinum.
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Veno-venous extracorporeal membrane oxygenation (ECMO) support surged during the COVID-19 pandemic. Our program changed the model of care pursuing to protect the multidisciplinary team from the risk of infection and to serve as many patients as possible. Patient-healthcare interactions were restricted, and the ECMO bed capacity was increased by reducing the ECMO specialist-patient ratio to 1:4 with non-ECMO trained nurses support. The outcomes worsened and we paused while we evaluated and modified our model of care. The ECMO bed capacity was reduced to allow a nurse ECMO-specialist nurse ratio 2:1 with an ECMO trained nurse assistant's support. Intensivists, general practitioners, nurse assistants, and physical and respiratory therapists were trained on ECMO. Tracheostomy, bronchoscopy, and microbiological molecular diagnosis were done earlier, and family visits and rehabilitation were allowed in the first 48 hours of ECMO cannulation. There were 35 patients in the preintervention cohort and 66 in the postintervention cohort. Ninety days mortality was significantly lower after the intervention (62.9% vs. 31.8%, p = 0.003). Factors associated with increased risk of death were the need for cannulation or conversion to veno arterial or veno arterio venous ECMO, hemorrhagic stroke, and renal replacement therapy during ECMO. The interventions associated with a decrease in the risk of death were the following: early fiberoptic bronchoscopy and microbiological molecular diagnostic tests. Increasing the ECMO multidisciplinary team in relation to the number of patients and the earlier performance of diagnostic and therapeutic interventions, such as tracheostomy, fiberoptic bronchoscopy, molecular microbiological diagnosis of pneumonia, rehabilitation, and family support significantly decreased mortality of patients on ECMO due to COVID-19.
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COVID-19 , Oxigenação por Membrana Extracorpórea , COVID-19/terapia , Cateterismo , Estudos de Coortes , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Pandemias , Estudos RetrospectivosRESUMO
Human cardiac valve allografts (HVAs) suffer injuries during the cryopreservation period. Here, we described structural, ultrastructural and functional damages suffered by HVAs after an increment of their cryostorage temperature (100 degree C). Two experimental groups of pulmonary and aortic HVAs were compared: cryopreserved (HVAcryo) and cryopreserved with temperature changes (HVAΔT). Transmission electron microscopy (TEM) was used to analyze valve fibroblasts and extracellular matrix morphology. Total collagen amount was estimated using two different methods and fibroblast viability was assessed measuring their oxygen consumption rate. Porcine heart grafts valves were used to set the techniques. Disorganized collagen network was seen in HVAΔT by TEM. Fibroblasts showed damages in the cellular membrane and many secretor vesicles. Mitochondria and chromatin were also altered. HVAΔT had less amount of collagen and fibroblasts showed an oxygen consumption rate markedly diminished compared to HVAcryo. The increment of 100 degree C suffered by HVAs caused damages that made them unsuitable for clinical purposes.
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Criopreservação , Valvas Cardíacas/ultraestrutura , Animais , Sobrevivência Celular , Cromatina/patologia , Temperatura Baixa , Colágeno/análise , Fibroblastos/ultraestrutura , Valvas Cardíacas/citologia , Valvas Cardíacas/fisiopatologia , Humanos , Mitocôndrias/patologia , Consumo de Oxigênio , Suínos , Transplante Homólogo/estatística & dados numéricosRESUMO
OBJECTIVE: To evaluate indoor air pollution in hospitality venues in Argentina. MATERIAL AND METHODS: PM2.5 levels were measured in a convenience sample of venues in 15 cities with different legislative contexts following a protocol developed by Roswell Park Cancer Institute. RESULTS: 554 samples were collected. Across all 5 smoke free cities the mean PM2.5 level was lower during daytime vs. evening hours, 24 vs. 98 PM2.5 respectively (p=.012). In the three cities evaluated before and after legislation, PM2.5 levels decreased dramatically (p<0.001 each). Overall, PM2.5 levels were 5 times higher in cities with no legislation vs. smoke free cities (p<0.001). In cities with designated smoking areas, PM2.5 levels were not statistically different between smoking and non-smoking areas (p=0.272). Non-smoking areas had significantly higher PM2.5 levels compared to 100% smoke free venues in the same city (twofold higher) (p=0.017). CONCLUSIONS: Most of the participating cities in this study had significantly lower PM2.5 levels after the implementation of 100% smoke free legislation. Hence, it represents a useful tool to promote 100% smoke free policies in Argentina.
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Poluição do Ar em Ambientes Fechados/análise , Poluição do Ar em Ambientes Fechados/legislação & jurisprudência , Monitoramento Ambiental , Política de Saúde/legislação & jurisprudência , Prevenção do Hábito de Fumar , Fumar/legislação & jurisprudência , Poluição por Fumaça de Tabaco/análise , Poluição por Fumaça de Tabaco/legislação & jurisprudência , Poluição do Ar em Ambientes Fechados/prevenção & controle , Argentina , Poluição por Fumaça de Tabaco/prevenção & controle , Saúde da População UrbanaRESUMO
UNLABELLED: In the present study we have analyzed the viability and metabolic competence of isolated rat hepatocytes subjected first, to subzero nonfreezing storage (up to 120 h at -4 degrees C) in modified University of Wisconsin (UW) solution with 8% 1,4-butanediol, and then to a normothermic rewarming step (KHR media, 37 degrees C, up to 120 min, carbogen atmosphere). Results were compared with hepatocytes stored up to 120 h at 0 degrees C in modified UW solution and with freshly isolated hepatic cells. We have found that only cell suspensions stored in subzero nonfreezing conditions were able to finish the rewarming period with a viability comparable with the control group. Also, we have investigated the enzyme activities and the relative expression at messenger RNAs levels of two of the Urea cycle (UC) enzymes: Carbamyl phosphate synthetase I (CPSI) and ornithine transcarbamylase (OTC), during 60 min of rewarming. Results were compared with the ammonium removal efficiency of the three groups. IN CONCLUSION: These data indicated that hepatocytes preserved under cold or subzero conditions up to 120 h followed by 60 min of rewarming, maintain UC enzymes at levels similar to freshly isolated hepatocytes, allowing their use in bioartificial liver devices.
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Butileno Glicóis/farmacologia , Criopreservação/métodos , Crioprotetores/farmacologia , Hepatócitos/efeitos dos fármacos , Soluções para Preservação de Órgãos/farmacologia , Ureia/metabolismo , Adenosina/farmacologia , Alopurinol/farmacologia , Animais , Carbamoil-Fosfato Sintase (Amônia)/genética , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa/farmacologia , Hepatócitos/enzimologia , Insulina/farmacologia , L-Lactato Desidrogenase/metabolismo , Masculino , Ornitina Carbamoiltransferase/genética , Ornitina Carbamoiltransferase/metabolismo , Propídio/metabolismo , Compostos de Amônio Quaternário/metabolismo , RNA Mensageiro/metabolismo , Rafinose/farmacologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
This work deals with the construction and performance of a device designed to measure the oxygen consumption by the liver during hypothermic perfusion in the rat model. Due to its simple design and the utilization of standard materials, it could serve to determine the role of oxygenation during hypothermic perfusion of the liver. The system consists of a reservoir containing the preservation solution, a peristaltic pump and an internal oxygenator made of silicone tube. A five ports manifold connects the circulation to the liver (inflow), to a hydrostatic manometer and to two sample ports; the liver outflow and temperature sensor or gas calibration. Finally the exit port connects the circulation fluid with an oxygen electrode. The preservation solution is pumped through the liver at a constant pressure (77 i 15 mm H2O) and a perfusion flow of 0.39 - 0.49 mL per min per g liver. To test the system, two to four hours perfusion experiments were performed, at temperatures of 5 and 10 degree C. Two preservation solutions were evaluated: Custodiol and Bes-Gluconate-Sucrose. The solubility of oxygen in the preservation solutions was determined, and the oxygen consumption by preserved rat livers was measured.
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Equipamentos e Provisões , Hipotermia/fisiopatologia , Fígado/fisiopatologia , Consumo de Oxigênio/fisiologia , Animais , Crioprotetores/farmacologia , Eletrodos , Gluconatos/farmacologia , Glucose/farmacologia , Hipotermia/patologia , Bombas de Infusão , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Manitol/farmacologia , Manometria , Cloreto de Potássio/farmacologia , Procaína/farmacologia , Ratos , Ratos Wistar , Análise de Regressão , Sacarose/farmacologia , TemperaturaRESUMO
RESUMEN Introducción: La miocardiopatía chagásica (MC) difiere de otras causas de insuficiencia cardíaca en múltiples aspectos, destacándose el riesgo de embolias sistémicas. Sin embargo, pocos estudios han evaluado el riesgo de eventos embólicos en pacientes anticoagulados con MC en comparación con otras miocardiopatías. Objetivo: Nuestro objetivo fue analizar la incidencia de embolias sistémicas en una cohorte de pacientes anticoagulados con diagnóstico de fibrilación auricular (FA) con y sin MC. Material y métodos: Se realizó un estudio de cohorte retrospectivo en hospital de cuarto nivel en Colombia durante el periodo 2014-2020. Se incluyeron todos los pacientes con diagnóstico de miocardiopatía de cualquier etiología y FA que estuvieran en régimen de anticoagulación. El resultado primario fue la incidencia de eventos embólicos. Se realizó un análisis de supervivencia mediante modelos de riesgos proporcionales de Cox ajustados. Un valor de p <0,05 se consideró significativo. Todas las pruebas estadísticas fueron de dos colas. Resultados: Se evaluaron 149 pacientes anticoagulados con miocardiopatía (mediana de edad: 71 años; mujeres: 30,20%). La incidencia acumulada de eventos embólicos fue significativamente mayor en los pacientes con MC (17,50%) en comparación con aquellos con otras miocardiopatías (4,95%), a pesar de que estos últimos tenían una puntuación CHA2DS2-VASc significativamente mayor (p=0,013). Tras el análisis multivariado, los pacientes con MC tuvieron un riesgo significativamente mayor de eventos embólicos independientemente de la puntuación CHA2DS2-VASc y del tipo de anticoagulante prescrito (HR 5,65; IC 95% 1,46-21,83; p=0,012). Conclusiones: La MC se asoció con un riesgo significativamente mayor de eventos embólicos, a pesar del tratamiento anticoagulante en ambos grupos. Se requiere más investigación para comprender el origen de este riesgo observado y traducir este conocimiento en indicaciones específicas de anticoagulación para pacientes con MC.
ABSTRACT Background: Chagasic cardiomyopathy (CC) differs from other heart failure causes in multiple aspects, highlighting the risk of systemic embolisms. However, few studies have evaluated the risk of embolic events in anticoagulated patients with CC compared with other cardiomyopathies. Objective: We aimed to analyze the incidence of systemic embolisms in a cohort of anticoagulated patients diagnosed with atrial fibrillation (AF) with and without CC. Methods: A retrospective cohort study was carried out at a fourth level hospital in Colombia during the period 2014-2020. All patients diagnosed with cardiomyopathy of any etiology and AF, who were on an anticoagulation regimen were included. The primary outcome was the incidence of embolic events. A survival analysis was performed using adjusted Cox proportional hazard models. A p-value <0.05 was considered significant. All statistical tests were two-tailed. Results: A total of 149 anticoagulated patients with cardiomyopathy were evaluated (median age: 71 years; women: 30.20%). The cumulative incidence of embolic events was significantly higher in patients with CC (17.50%) compared with those presenting other cardiomyopathies (4.95%), despite that the latter had a significantly higher CHA2DS2-VASc score (p=0.013). After multivariate analysis, patients with CC had a significantly higher risk of embolic events regardless of the CHA2DS2-VASc score and the type of anticoagulant prescribed (HR 5.65; 95% CI 1.46-21.83; p=0.012). Conclusions: Chagasic cardiomyopathy was associated with a significantly higher risk of embolic events, despite anticoagulation therapy in both groups. More research is required to understand the origin of the risk observed in order to translate this knowledge into specific indications for anticoagulation in patients with CC.
RESUMO
This work deals with the construction and performance of a hollow fiber-based minibioreactor (MBR). Due to its simple design and the utilization of standard materials, it could serve as a suitable tool to evaluate the behavior and performance of cold preserved or cultured hepatocytes in bioartificial liver devices. The system consists of 140 fiber capillaries through which goat blood is pumped at a flow of 9 mL/min. The cell compartment contains 90 x 10(6) rat hepatocytes (volume 10 mL) and an internal oxygenator made of silicone tubing. To test the in vitro function of the system, 2-h perfusion experiments were performed, the evolution of hematocrit, plasma and extra-fiber fluid osmolality, and plasma urea and creatinine concentrations were evaluated. The detoxication efficiency of an ammonia overload was tested, showing that the system has enough capacity to remove ammonium. Also, the MBR oxygen transfer capacity to hepatocytes was tested, showing that the cells received an adequate oxygen supply.
Assuntos
Reatores Biológicos , Cabras/sangue , Hepatócitos/metabolismo , Fígado Artificial , Amônia/sangue , Animais , Sobrevivência Celular , Creatinina/sangue , Desenho de Equipamento , Hematócrito , Masculino , Concentração Osmolar , Oxigênio/sangue , Ratos , Ratos Wistar , Fatores de Tempo , Ureia/sangueRESUMO
AIM: To determine the influence of the construction design over the biological component's performance in an experimental bio-artificial liver (BAL) device. METHODS: Two BAL models for liver microorgans (LMOs) were constructed. First, we constructed a cylindrical BAL and tested it without the biological component to establish its correct functioning. Samples of blood and biological compartment (BC) fluid were taken after 0, 60, and 120 min of perfusion. Osmolality, hematocrit, ammonia and glucose concentrations, lactate dehydrogenase (LDH) release (as a LMO viability parameter), and oxygen consumption and ammonia metabolizing capacity (as LMO functionality parameters) were determined. CPSI and OTC gene expression and function were measured. The second BAL, a "flat bottom" model, was constructed using a 25 cm2 culture flask while maintaining all other components between the models. The BC of both BALs had the same capacity (approximately 50 cm3) and both were manipulated with the same perfusion system. The performances of the two BALs were compared to show the influence of architecture. RESULTS: The cylindrical BAL showed a good exchange of fluids and metabolites between blood and the BC, reflected by the matching of osmolalities, and glucose and ammonia concentration ratios after 120 min of perfusion. No hemoconcentration was detected, the hematocrit levels remained stable during the whole study, and the minimal percentage of hemolysis (0.65% ± 0.10%) observed was due to the action of the peristaltic pump. When LMOs were used as biological component of this BAL they showed similar values to the ones obtained in a Normothermic Reoxygenation System (NRS) for almost all the parameters assayed. After 120 min, the results obtained were: LDH release (%): 14.7 ± 3.1 in the BAL and 15.5 ± 3.2 in the NRS (n = 6); oxygen consumption (µmol/min·g wet tissue): 1.16 ± 0.21 in the BAL and 0.84 ± 0.15 in the NRS (n = 6); relative expression of Cps1 and Otc: 0.63 ± 0.12 and 0.67 ± 0.20, respectively, in the BAL, and 0.86 ± 0.10 and 0.82 ± 0.07, respectively, in the NRS (n = 3); enzymatic activity of CPSI and OTC (U/g wet tissue): 3.03 ± 0.86 and 222.0 ± 23.5, respectively, in the BAL, and 3.12 ± 0.73 and 228.8 ± 32.8, respectively, in the NRS (n = 3). In spite of these similarities, LMOs as a biological component of the cylindrical BAL were not able to detoxify ammonia at a significant level (not detected vs 35.1% ± 7.0% of the initial 1 mM NH4 + dose in NRS, n = 6). Therefore, we built a second BAL with an entirely different design that offers a flat base BC. When LMOs were placed in this "flat bottom" device they were able to detoxify 49.3% ± 8.8% of the initial ammonia overload after 120 min of perfusion (n = 6), with a detoxification capacity of 13.2 ± 2.2 µmol/g wet tissue. CONCLUSION: In this work, we demonstrate the importance of adapting the BAL architecture to the biological component characteristics to obtain an adequate BAL performance.