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Se presenta el caso clínico de una paciente de 10 años diagnosticada con miocardiopatía dilatada, quien registró valores en el índice internacional normalizado (International Normalized Ratio, INR) superiores a 10 con la dosis estándar de acenocumarol, además de otros valores que indicaban el estado incoagulable, lo que obligó a suspender y reiniciar el tratamiento en varias ocasiones. Después de más de 30 días de tratamiento, sorprendentemente se lograron los niveles esperados y estables en el INR con la mitad de a dosis recomendada para una paciente de su edad y peso. Se decidió hacer un análisis farmacogenético retrospectivo del caso mediante RT-PCR con sondas TaqMan™ que incluyó cinco polimorfismos de un solo nucleótido y distinto grado de asociación con la dosis-respuesta a los fármacos antivitamínicos K (AVK): rs2108622 (gen CYP4F2), rs9923231, rs7294 (gen VKORC1), rs1799853 y rs1057910 (gen CYP2C9). La paciente resultó ser homocigota para el rs9923231 (VKORC1) y heterocigota para el rs2108622 (CYP4F2). Se ha evidenciado a nivel nacional e internacional que este perfil genético está fuertemente asociado con una necesidad de dosis menores de antivitamínicos K. En conclusión, el análisis farmacogenético confirmó que la condición genética de la paciente, la cual conlleva una baja expresión de la enzima VKORC1 (blanco terapéutico de los antivitamínicos K), hacía predecible la necesidad de una dosis menor a la establecida según los protocolos clínicos recomendados por la Food and Drug Administration (FDA) y PharmGKB™ para los fármacos cumarínicos.

BackgroundVitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables.ObjectiveThe authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patientsMethodologyDNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0–3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for VKORC1 (rs9923231), VKORC1 (rs7294), GGCx (rs11676382), CYP4F2 (rs2108622), ABCB1 (rs1045642), CYP2C9*2 (rs1799853), ApoE (rs429358), and CYP2C9*3 (rs1057910).ResultsThe clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were VKORC1 (rs9923231), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), explaining for another 37% of the variability.ConclusionWe developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included VKORC1, CYP2C9*2, and CYP2C9*3 polymorphisms, as well as age, sex, BMI, and initial INR.

Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. It is well known that polymorphisms in pharmacokinetic and pharmacodynamic proteins related to coumarins (especially warfarin) influence response to these drugs. This work analyzed the impact of CYP2C19*2 ( rs4244285 ), CYP1A2*1F ( rs762551 ), GGCx ( rs11676382 ), CYP2C9*2 ( rs1799853 ), CYP2C9*3 ( rs1057910 ), CYP4F2 ( rs2108622 ), VKORC1 ( rs9923231 ), VKORC1 ( rs7294 ), CYP3A4*1B ( rs2740574 ), and ABCB1 ( rs1045642 ) polymorphisms on time to therapeutic range for oral anticoagulants in 304 Chilean patients. CYP2C9*3 polymorphisms were associated with time to therapeutic range for acenocoumarol in Chilean patients, and the CYP4F2 TT genotype, MDR1 A allele, CYP1A2 A allele, and CYP3A4 T allele are promising variants that merit further analysis. The presence of polymorphisms explained only 4.1% of time to therapeutic range for acenocoumarol in a multivariate linear model. These results improve our understanding of the basis of ethnic variations in drug metabolism and response to oral anticoagulant therapy. We hope that these findings will contribute to developing an algorithm for VKA dose adjustment in the Chilean population in the near future, decreasing the frequency of stroke, systemic embolism, and bleeding-related adverse events.

Warfarin and acenocoumarol are used in various cardiovascular disorders to improve the prognosis of patients with thromboembolic disease. However, there is a lack of substantial efficacy and safety data on antithrombotic prophylaxis in several countries, particularly in Latin America. The aim of this study was to provide information about the efficacy of anticoagulants in Chilean patients. Data were collected from databases of the Western Metropolitan Health Service, Santiago, Chile. We identified 6280 records of patients receiving anticoagulant treatment. The three most common diagnoses were rhythm disorder (43.7%), venous thrombosis (22%), and valvular prosthesis (10.7%). The majority of patients (98.5%) received acenocoumarol while 1.5% of patients received warfarin, at weekly therapeutic doses of 13.6 mg and 30.4 mg, respectively. For total diagnoses, the median time in the therapeutic range was 50%. However, better results, 66.7%, were observed when a telemedicine strategy was used only in Santiago Province. Our findings emphasize that in Chile, where the number of patients receiving anticoagulant treatment increases every year, telemedicine, by committed teams, improves the use of oral anticoagulants and is able to increase quality indicators of anticoagulant treatment care.

Introducción: Recientemente la gastroenterología pediátrica ha avanzado en el estudio de la fisiopatología de los trastornos motores. Objetivo: Realizar una revisión narrativa de los estudios de motilidad en pediatría, con descripción del procedimiento, las indicaciones y limitaciones en los niños. Metodología: Revisión bibliográfica (PubMed, Medline) de estudios manométricos en pediatría entre los años 2002 y 2020. Resultados: Las indicaciones de la manometría esofágica son diagnosticar trastornos motores, alteraciones anatómicas y síntomas postquirúrgicos y relacionar alteraciones de la motilidad con el tránsito del bolo. Las dificultades en la edad pediátrica radican en el costo de los equipos de alta resolución, contar con catéteres pediátricos, falta de colaboración de los niños pequeños y necesidad de colocar el catéter con sedación. La manometría anorrectal es el procedimiento manométrico más empleado en pediatría. Actualmente hay mejor entendimiento con relación al equipo, metodología empleada y valores de referencia. La manometría antroduodenal estudia los trastornos de la motilidad gástrica e intestinal. La colocación del catéter requiere procedimientos invasivos o radiación. Los equipos son costosos, al igual que los catéteres pediátricos y su disponibilidad es limitada. Lo mismo ocurre con la manometría colónica, un estudio valioso para el diagnóstico de trastornos graves de la defecación. Conclusiones: Las indicaciones de los estudios manométricos, su utilidad y la técnica de realización en pediatría están claramente establecidas. Las limitaciones surgen de aspectos concernientes al paciente pediátrico: falta de colaboración de los niños pequeños, escasa disponibilidad de catéteres pediátricos, dificultades en la interpretación de los estudios y falta de valores de referencia en población pediátrica.

Oxidative stress is thought to contribute to the aetiology of neurological disorders such as Parkinson’s disease. Ascorbate (vitamin C) is a potent antioxidant and is associated with neurological and cognitive function. In this study we assessed the ascorbate status of a cohort of people with Parkinson’s disease (n = 215), aged 50–90 years, compared with a cohort of age matched healthy controls (n = 48). The study sample’s cognitive status ranged from normal to mild cognitive impairment and dementia. There was no difference between the Parkinson’s disease and healthy control groups with respect to mean ascorbate status, however, a higher proportion of participants with Parkinson’s disease had hypovitaminosis C (i.e., r = 0.14, p = 0.045). Participants with hypovitaminosis C had significantly lower MoCA scores relative to participants with ascorbate concentrations >23 µmol/L (p = 0.014). Ascorbate concentrations were significantly lower in the cognitively impaired subgroup compared with the normal cognition subgroup in the Parkinson’s disease cohort (p = 0.03). In contrast, urate showed an inverse correlation with cognitive function (r = −0.19, p = 0.007), with higher urate concentrations observed in the cognitively impaired subgroup compared with the normal cognition subgroup (p = 0.015). There was an inverse association between ascorbate status and urate concentrations (r = −0.15, p = 0.017). Plasma protein carbonyls, a measure of systemic oxidative stress, were not significantly different between the Parkinson’s disease cohort and healthy controls, and there was no association with cognitive function (r = 0.09, p = 0.19) or with ascorbate status (r = −0.05, p = 0.45). Overall, our study showed ascorbate status was positively associated with cognitive function in Parkinson’s disease, suggesting that longitudinal studies investigating the temporal sequence of cognitive decline and ascorbate status are warranted.

The following study has the primary objective of identifying the major competitive advantages owned by Brazilian beef processing plants in their internationalization process. In order to reach it, it was carried out an exploratory research, based on the survey of official data and publications concerning world’s beef cattle production, followed by a literature review and finally, by a single case study. This case study was conducted through an interview with former employee of Redenção Frigorífico do Pará Ltda. The obtained results allowed the identification of the major competitive advantages of the studied company in its internationalization process, such as the raw material quality and availability, production scale, Brazilian cattle’s extensive production system, and control and prevention of main cattle diseases. It was concluded that Brazilian beef production plants really have competitive advantages within the internationalization process context, some of them practically observed in the studied company, and others that can be effectively corroborated by future studies.

O presente trabalho teve como objetivo a identificação das principais vantagens competitivas apresentadas pelos frigoríficos brasileiros em seu processo de internacionalização. Para atingi-lo, foi realizada uma pesquisa de caráter exploratório, fundamentada em levantamento de dados oficiais e em publicações do setor pecuário nacional, associada a uma revisão de literatura sobre o tema e a um estudo único de caso. O estudo de caso foi elaborado com base em entrevista com ex-funcionário da empresa Redenção Frigorífico do Pará Ltda. Os resultados obtidos permitiram identificar as principais vantagens competitivas da empresa estudada em seu processo de internacionalização: a qualidade e a disponibilidade da matéria prima; a escala de produção; o sistema de produção extensivo da pecuária nacional; o controle de enfermidades do rebanho. Concluiu-se que, de fato, os frigoríficos brasileiros apresentam caracaterísticas que lhes conferem diferenciação dentro do contexto da internacionalização ― algumas verificadas na própria empresa estudada e outras que poderão ser devidamente comprovadas por meio de estudos futuros.